Genomics Revolution

Genomics Revolution 

Guest Hosts: Abbey Anderson & Samantha Mansfield 

Episode 46: Hepacivirus (Hepatitis C)

 
Script:

     Hello! This is Sammie and Abbey coming at you live from a safe social distance! Today we are here to talk to you about Hepacivirus which is commonly known as Hepatitis C virus. We are going to spend some time talking about when and how the virus was discovered, the reasons that we should care about this virus, the genome of Hepatitis C, and key findings about HepC virus. 

Sammie: Every story starts somewhere and the uniqueness of this virus is how it was discovered. This virus was first named in 1989. Doctors knew that this might have had something to do with blood transfusions, but it was called non-A, non-B hepatitis because they could not pinpoint the exact virus down. Later it became known that there were several different genotypes of the hepatitis C virus. This virus is widespread and curable now a days if caught early enough. The spread of this virus occurs by sexual intercourse, blood to blood contact, or improperly sterilized equipment (2). While we now understand how to take precautions against HepC, many people today are still infected by the virus through needle sharing. With the present opioid epidemic, especially in our great state of Ohio, we must understand the vast impacts that drug sharing can cause. This leads into why we should care about the virus that turns into a  serious disease. 

Abbey: According to the CDC, there are 2.4 million people in the United States alone living with hepatitis C. Worldwide, HepC affects more than 170 million people. This virus is often ignored until it is too late. There are two phases of hepatitis C which occurs when the person is infected but shows no symptoms. Even if there are symptoms, most people never realize until they are diagnosed with liver disease. According to the San Francisco Department of Health, in 15-40% of the persons with acute hepatitis C, the immune system will fight off the infection and there will be no presence of the virus within 6 months and the liver heals completely. In most other people, the immune system cannot clear the virus and after 6 month time window this is then classified as chronic hepatitis C. This disease will cause the liver to become more and more inflamed and scarred over several years. According an article written by the University of Texas  Hepatitis C is the leading cause of liver cancer (5). 

Sammie: According to a microbiology textbook edited by Dr. Tan Seng-Lair, The hepatitis C virus belongs to the family Flaviviridae. This family genome consists of a positive strand RNA molecule that ranges in size from  9.6 to 12.3 thousand nucleotides.The Hepatitis C virus open reading frame is known to contain 9,024-9,111 nucleotides, depending on the genotype. It is a double stranded RNA molecule. Hepatitis C virus encodes a single polyprotein, and this is processed to generate 10 polypeptides (1). The number of predicted coding proteins is 11. 

Abbey: Now it is time to talk about why sequencing this viral genome helped our understanding of Hepatitis C. Remember those genotypes mentioned earlier? Yep, they really come into play here. From sequencing the HepC virus, scientists have discovered that this virus exists in 8 different genotypes, all with different geographical distributions according to a study that was looking at where the highest burden of HepC occurs in Southeast Asia (3).  The analysis of Hepatitis C Virus nucleotide sequences has worked as an epidemiological marker, allowing scientists to trace the source of HepC infection within a given population (6). Until 2019, it was believed that HepC only existed in 6 genotypes with more than 50 subtypes. The best part is, not all of these 8 genotypes have been sequenced! In case you are interested in classifying the next Hepatitis C type, the complete genome sequence must differ from other sequences by 30% in genotype or by 15% in subtype (4). From sequencing these genomes, researchers have also been able to determine which genotypes and subtypes are more prevalent in specific regions around the world. They often follow patterns of human migration. For example, subtypes 1a, 1b, 2a, 2b, 2c, and 3a are found worldwide and make up the largest portion of HepC infections (4). Other subtypes, recall that there are over 50, are extremely rare and are found in restricted geographical locations such as West Africa, Central Africa, India, and even Canada.

Sammie: Finally, we should mention the most important use of sequencing the HepC genome...HepC treatments. According to the National Institute of Health, by having a sequenced genome, scientists began to target different genes in order to develop drugs that would combat Hepatitis C. Some drugs target the gene responsible for the activity of HepC polymerase, the enzyme that aids in replication of the virus. Other drugs target genes that encode the virus’s structural proteins. 

Abbey:  While it may seem that we know a lot about Hepatitis C virus today, we are still a long ways away from a vaccine. Because this virus mutates so rapidly and exists in so many genotypes, making a vaccine is more complicated than it seems. We hope you enjoyed learning a little bit more about Hepatitis C, and remember, make sure you avoid needle sticks! See you next time on Genomics Revolution. 

References:

1)    Dubuisson, J. (2007). Hepatitis C virus proteins. World Journal of Gastroenterology, 13(17), 2406. doi: 10.3748/wjg.v13.i17.2406

2)    Hepatitis C. (n.d.). Retrieved April 5, 2020, from https://www.sfcdcp.org/infectious-diseases-a-to-z/hepatitis-c/

3)    Ngoc, C. L., Thanh, T. T. T., Lan, P. T. T., Mai, T. N., Hoa, T. N., My, N. N., … Vizions. (2019, March 19). Differential prevalence and geographic distribution of hepatitis C virus genotypes in acute and chronic hepatitis C patients in Vietnam. Retrieved April 5, 2020, from https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0212734#sec005

4)    Spitz, N., Barros, J., doO, K., Brandao-Mello, C., & Araujo, N. (2019). The First Complete Genome Sequences of Hepatitis C Virus Subtype 2b from Latin America: Molecular Characterization and Phylogeographic Analysis . Viruses, 11(11). doi: 10.3390/v11111000

5)    Underferth, D., & MD Anderson Cancer Center. (2019, May 8). Hepatitis C and liver cancer: What to know. Retrieved April 5, 2020, from https://www.mdanderson.org/publications/focused-on-health/HepatitisC-liver-cancer-What-you-need-to-know.h16Z1591413.html

6)    Zein, N. N. (2000). Clinical Significance of Hepatitis C Virus Genotypes. American Society for Microbiology. doi: https://dx.doi.org/10.1128/cmr.13.2.223-235.2000

Genomics Revolution

Guest Hosts: Ciara Love & Cara Katzendorn

Episode 45: Hepatitis B Virus

Script:

     Hi, my name is Ciara and today we’re going to talk about a virus called Hepatitis B. This virus is a type of species in the orthohepadnavirus genus as well as a member of the hepadnaviridae family. This virus causes a world-wide known disease called Hepatitis B or HBV. HBV causes liver cancer and the vaccine that was invented for Hepatitis B was one of the first anti-cancer vaccine. The virus was discovered in 1965 by Dr. Baruch Blumberg, which he had won a Nobel Prize for. He worked with a microbiologist named Irvine Millman, to help develop a blood test for the virus that blood centers were using in 1971. The first vaccine was originally the virus treated by heat, and then later in 1986 genetically engineered Hepatitis B vaccines were created. We should care about understanding this virus because it affects everyone and some people carry this virus their whole lives. This virus is a partial double dna stranded molecule that usually replicates by reverse transcription and has between 3182-3248 base pairs depending on the genotypes.

The hepatitis B genome includes four open reading frames for viral proteins. These four groups are surface antigens, core protein, polymerase, and protein X whose function is unclear but may be connected to this virus’s influence on the development of liver cancer. Therapies and vaccines continue to advance in the hopes of finding cure for this disease. In 2015, a study published in the Journal of Clinical microbiology demonstrated researchers improving techniques of identifying this virus throughout all 10 different genotypes found in patients. They designed a mix of primers based on sequencing from over 5000 Hbv patients that would help in creating a more analytically sensitive PCR amplification for detection of this virus. This may be used as a universal detection method for all genotypes of this disease.

In 2012 researchers set out to identify the functional effects of HBV viral integration into the human genome, in hopes of indicating how this virus connects with liver cancer. They found that the virus had many possible effects by insertional mutagenesis, viral promoter-driven transcriptional up-regulation, and genomic instability. This study opens possibilities for future studies that will hopefully be able investigate medicines to prevent the development of liver cancer in HBV patients.

Research continues to develop our understanding of this virus and the diseases associated with infection, and a cure for patients in on the horizon.

Resources:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5313610/

https://www.ncbi.nlm.nih.gov/pubmed/12480564

https://www.hepb.org/prevention-and-diagnosis/vaccination/history-of-hepatitis-b-vaccine

https://hbvdb.lyon.inserm.fr/HBVdb/HBVdbGenome

http://garfield.library.upenn.edu/classics1979/A1979HW50100001.pdf

https://www.ncbi.nlm.nih.gov/pubmed/26112647

https://jcm.asm.org/content/53/6/1831

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3317142/?report=reader#!po=46.4286

Genomics Revolution

Kiyana Caver & Brittany Weaver

Genetics Podcast Transcript

Episode 44: Poliovirus

Script:

      Hello, I am Kiyana & I am Brittany and we will discuss the virus poliovirus which causes polio.  Polio can also be known as poliomyelitis.  It stems from the Greek meaning of an inflammation of the gray matter.  In the early 20thcentury there weren’t many diseases that had parents worried about the health and wellbeing for their children.  However, poliomyelitis is something that parents were fearful of their children getting.  Poliomyelitis was a disease that was more common to catch during the summer as that is when polio was more likely to come about, in warmer weather.  This disease is very contagious and it is caused by a virus that attacks the nervous system, it also can lead to spinal cord and or brain stem paralysis if it is not treated soon.  The people that are mostly affected by it are younger children, usually children become affected with the disease before they turn 5 years old (7 & 6).  Polio was most likely spread through contact between people by nasal and oral secretions and by coming into contact with contaminated feces.  Polio enters through the mouth, multiplies through the digestive tract where it continues to multiply.  Polio was discovered in 1908 by Karl Landsteiner and Erwin Popper.  Poliovirus was discovered as scientists were proving that it was not a bacterium that had been causing paralysis, but instead it was a virus (5).  Despite it being discovered it the early 1900’s, poliovirus did not peak in the United States until around 1952 when almost 60,00 cases had sparked throughout the United States. 

Poliovirus is a RNA genome with a protein capsid made up of one single RNA positive sense stand, that is about 7500 nucleotides long.  There is one primary RNA molecule in the genome, which has been shown to have 8 unused start codon sites that are in front of the active AUG start codon.  The molecule also has 23 RNA hairpin secondary structures (3).  Poliovirus has one main cleavage of a precursor polypeptide called NCVP 1 which encodes for proteins VP 1, 2, 3, and 4 (1).  Poliovirus originated from a single precursor molecule called NCVPOO [noncapsid viral protein (NCVP] (2).  Poliovirus is a well known and studied virus because between the period of the 1940’s-1950’s the virus was at its most epidemic (8).  Polio had crippled around 35,000 people every year in the US alone.  A study was preformed in 1994-1995 that showed over 1 million people had survived poliovirus but, over 443,000 people reported having been paralyzed, as it affects a persons nervous system.  During the epidemic when it was at its highest affect there were reports of about 27,000 people reporting paralyzation and about 6,000 deaths.  When poliovirus was sequenced it led to many discoveries that affected the treatment and prevention of polio in the world.  Research found that there were 3 serotypes of poliovirus that caused paralysis in diffferent ratios, type 1 was the most paralytic and accounted for about 80% of paralyzation, type 2 had 8% and type 3 had 13%.  This finding was important because it allowed for more focus to be pulled onto why one type was more paralytic than others. Another key finding was that of inactivated poliovirus also known as IPV being introduced for polio in 1955 and oral poliovirus also known as OPV in 1961.  These were both used to protect immunized patients and it was found that OPV could spread from the vaccinated to close companions when in contact, increasing the immunity in the US, which was seen when the number of annual inciddences fell drastically.  Knowing that OPV was a good way of immunization it was studied along with the wild poliovirus sequence to see how many doses of OPV was approximately needed to eradicate wild poliovirus.  The US and other countries tested the possibility of eradicating the wild poliovirus and was first succesful in Cuba through the eradication of wild poliovirus.  It was found that if a child by the age of 12 months had 3 doses of OPV that percentage of cases of wild poliovirus decreases.  The eradication of all indigenous wild poliovirus occurred in 1991 (4).

This is Brad Goodner and I need to step in with an add-on to Brittany’s last sentence.  After success in Cuba, the eradication of wild poliovirus in 1991 was from the entire Western Hemisphere through an organized immunization effort using the oral poliovirus vaccine.  Since then, efforts have continued worldwide and we are so close to complete eradication of polio that immunization programs have switched from the oral vaccine to the inactivated vaccine to prevent OPV-derived shedding of live virus that might cause rare infections on non-immunized individuals.  Hopefully, we are only a few years away from saying goodbye to this small but devasting virus.

This has been our genomic podcast on poliovirus, thank you for listening and we hope you now know more about poliovirus.

References:

1.     Rekosh, David. “Gene Order of the Poliovirus Capsid Proteins.” Journal of Virology, vol. 9, no. 3, Mar. 1972, pp. 479–487., doi:10.1128/jvi.9.3.479-487.1972.

2.     Nomoto, A., et al. “Complete Nucleotide Sequence of the Attenuated Poliovirus Sabin 1 Strain Genome.” Proceedings of the National Academy of Sciences, vol. 79, no. 19, Jan. 1982, pp. 5793–5797., doi:10.1073/pnas.79.19.5793.

3.     Simoes, E A, and P Sarnow. “An RNA Hairpin at the Extreme 5 End of the Poliovirus RNA Genome Modulates Viral Translation in Human Cells.” Journal of Virology, vol. 65, no. 2, Feb. 1991, pp. 913–921., doi:10.1128/jvi.65.2.913-921.1991.

4.     Nathanson, N., and O. M. Kew. “From Emergence to Eradication: The Epidemiology of Poliomyelitis Deconstructed.” American Journal of Epidemiology, vol. 172, no. 11, 26 Oct. 2010, pp. 1213–1229., doi:10.1093/aje/kwq320.

5.     “NMAH: Polio: The Polio Genome.” NMAH | Polio: The Polio Genome, 1 Feb. 2005, https://amhistory.si.edu/polio/virusvaccine/livingchem.htm

6.     “Polio.” Mayo Clinic, Mayo Foundation for Medical Education and Research, 9 Dec. 2017, www.mayoclinic.org/diseases-conditions/polio/symptoms-causes/syc-20376512.

7.     “Poliomyelitis.” World Health Organization, World Health Organization, www.who.int/news-room/fact-sheets/detail/poliomyelitis.

8.     “Post-Polio Syndrome Fact Sheet.” National Institute of Neurological Disorders and Stroke, U.S. Department of Health and Human Services, www.ninds.nih.gov/disorders/patient-caregiver-education/fact-sheets/post-polio-syndrome-fact-sheet.

Genomics Revolution
Mit Patel and Andrew Pemberton
Episode 43: Variola Virus (Cause of smallpox)

Script:
     Welcome to the Genomic Revolution Podcast! This is Mit Patel and Andrew Pemberton from the 2020 Hiram College Genetics course hosting this episode on an orthopoxvirus known as the Variola virus. This virus causes the disease that many of our parents or grandparents may have gotten when they were younger but rather for us millennials we are vaccinated for it. The variola virus or VARV causes the disease smallpox. However, there are some mysteries as to how it originated. According to Igor Babkin, an author of The Origin of the Variola, the descriptions of smallpox can be seen in ancient literature books from India which were written in 6th or even 15th century BC. Historical evidence shows that smallpox has been seen in many countries including India, china, egypt, and even parts of europe. The variola virus has been proven to be only transmitted between sensitive people but it does not show any signs of affecting an animal. Therefore as a result, the majority of the sensitive people will have two outcomes: be immune or die which will cause the virus to fade. Many researchers have come to conclude that animal domestication, land farming, and large human settlements about 6000 to 10000 years ago truly caused the emergence of smallpox (Babkin, 2015).

Now you listeners may be wondering why I should care about a disease that we already have a vaccination for? But, truly understanding the history and information on how the resolution was found, gives the idea of how important this virus is. When smallpox was around, it was certainly a devastating disease. On average, out of 10 people about 3 of them would die. And due to this, control efforts started to be implemented. One of the first methods was the use of variolation. Variolation, named after the variola virus, was first used in Asia where a small dried smallpox scab was blown into the nose of an individual. This individual would then contract the disease but a milder form. At the end, the individual would be immune to smallpox. Due to this, only about 1%-2% percent died rather than 30%. By 1700, variolation had spread to India, Africa, and the Ottoman empire. Europeans and Americans tended to variolate by puncturing the skin (CDC, 2016).

On the other hand comes the factual information. So the variola virus is a double stranded DNA with a length of approximately 190 kbp, specifically 186,102 base pairs. A 102 kbp is compromised for a central conserved domain, which encodes for multiple different proteins. The virus encodes for about 200 proteins altogether all having different functions. About 80 of those encoded proteins are located in the terminal regions of the genome, where proteins related to host immune invasion are encoded.

The variola virus belongs to the genus of ​Orthopoxvirus a​ nd is in the family of Poxvirus (Babkin and Babkina). Research done by Mackett and Archard performed DNA sequencing of several organisms from the genus of Orthopoxvirus (Mackett and Archard). Using restriction endonuclease, they analyzed the genome structure of several viruses and discovered that there is a central conserved region in Orthopoxvirus organisms (Mackett and Archard). It was determined that these highly conserved regions are important to vital function of the virus, including DNA replication and repair, transcription and such (Mackett and Archard). The sequenced DNA also showed variation of the terminus end. This variation is how the Orthopoxvirus viruses vary and is how monkeypox virus infects monkeys and why variola virus is specific to humans (Mackett and Archard). Genome sequencing of the variola virus and closely related virus has revealed which regions of the DNA determine function of the Orthopoxvirus including the variola virus.

Another area where the genome sequence of Variola Virus has been used is to create a phylogenetic tree, or a tree that shows evolutionary relationships among different organisms and in our case viruses. In a paper published by Smithson and other authors, their core group members used one of the first sequenced ancient variola virus genomes. With this, they removed sequencing tags and conducted manual gap-spanning reads. This new assembly was used along with other orthopoxvirus genomes like camelpox and taterapox to determine the last common ancestor of the VARV virus. Their analysis of these different genomes including variola virus lead them to conclude that single nucleotide polymorphisms and amino acid changes in the vaccinia virus ortholog associated to the VARV host specificity and virulence. Furthermore, it was found that these traits were introduced prior to the rise of recent pox viruses. An interesting fact from this paper is that when comparing the ancient and modern VARV genome sequences there is measurable drift in Adenine and thymine richness (Smithson, 2017).

A large worry of many is the reemergence of the smallpox virus. In a paper by Theves and others, they exhumed bodies from an elite burial dating back to 1730s to 1740s, due to the burial time being in the winter and lack of trauma, the authors hypothesized that they died because of a pathogen. At first they thought it might have been a bacterial pathogen, but when they could not find any evidence they searched for a virus (Thèves et al.). After some searching they were able to identify some DNA fragments that were from the poxvirus family, since they were humans, it was smallpox (Thèves et al.). The worry of reemergence prompts researchers to sequence all variations of the variola virus, even ancient variations, in order to have the best possible chance to combat the variola virus if it were to mutate and evolve to infect people again.

We would like to thank you all for listening and we would also like to thank Professor Goodner for allowing us to join Genomics Revolution! We hope that you got a great understanding about the variola virus.

References:
Babkin, Igor, and Irina Babkina. "The Origin Of The Variola Virus". Viruses, vol 7, no.3, 2015, pp. 1100-1112. MDPI AG, doi:10.3390/v7031100. Accessed 9 Apr 2020.

“History of Smallpox.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 30 Aug. 2016, www.cdc.gov/smallpox/history/history.html.

Mackett, M, and L.C. Archard. "Conservation And Variation In Orthopoxvirus Genome Structure". General Virology, vol 45, no. 3, 1979, pp. 683-701., Accessed 4 Apr 2020.

Smithson, Chad et al. “Re-Assembly and Analysis of an Ancient Variola Virus Genome.” Viruses vol. 9,9 253. 8 Sep. 2017, doi:10.3390/v9090253

Thèves, C. et al. "The Rediscovery Of Smallpox". Clinical Microbiology And Infection, vol 20, no. 3, 2014, pp. 210-218. Elsevier BV, doi:10.1111/1469-0691.12536.

Genomics Revolution

Brianna Bays and Melika King 

Episode 42

Influenza Type B Virus

Script:

     Welcome to Genomics Revolution.  This is Brianna Bays and Melika King from the 2020 Hiram College Genetics course hosting this episode over Influenza virus type B commonly known as the flu virus.  The common symptoms are fever, muscle aches, headache, lack of energy, sore throat, and nasal congestion (1).  Complications can rise due to immune status and underlying medical conditions (1).

In 1892 two physicians Richard Pfeiffer and Shibasaburo Kitasato worked at a lab in Berlin claimed discovery of a new bacterium (2).  Since the flu is seasonal, other people had a hard time investigating the correlation between influenza B and the true cause of the illness.  Until the next outbreak in 1918 when Peter Olitsky and Frederick Gates provided strong evidence to prove influenza B was the cause (2).  Modern techniques used to identify influenza B are reverse transcription polymerase chain reaction (RT-PCR), immunofluorescence assays and rapid molecular assays (1).

All human influenza viruses are enveloped negative-strand RNA viruses with segmented genomes containing seven to eight gene segments (3).  Influenza B has eight and it comprises about 14,000 nucleotides (3).  This genome has four proteins in the envelope: hemagglutinin(HA), neuraminidase (NA), NB, and BM2 (3).  HA and NA are surface proteins and these are considered antigenic sites where the body’s immune system develops antibodies to bind to (3).  To test for antigenic changes, scientists can use hemagglutinin inhibition assay essentially seeing how well antibodies bind to it making the influenza virus inactive.  The NB protein is believed to be an ion channel (3) and the BM2 protein is a proton channel that is important for the uncoating process (4).  Uncoating refers to the deliverying of the viral genome to the host cell for replication. Influenza viruses recognizes N-acetylneuraminic (sialic) acid on the host cell surface (4).  N-acetylneuraminic are found on glycoconjugates (5).

Having the knowledge about this genome, scientists then can compare it to other viral genomes of influenza B to see if there are any genetic variations.  That allows them to create a more effective vaccine.  To look at the genome the CDC uses techniques like ‘the Sanger reaction’ and advanced molecular detection (1).  It is important to understand influenza B just like any other virus because it can be prevented from spreading and helps scientists come up with an effective treatment.  This virus is commonly seen in humans and seals so we do not see as many genetic changes as we do with influenza A viruses (1).  Currently influenza B viruses are classified into two genetic lineages - Yamagata and Victoria (6).

 It is important to understand influenza B just like any other virus.  Having scientific knowledge about this virus and knowing its genome can help correlate to studies of viruses that may come about in the future and help us gain insight about their mechanisms, based on the genomes' similarities and differences.  Knowing the mechanisms also allows scientists to come up with an effective treatment not just for Influenza B but other viruses as well.  Lastly, everyone having an understanding of how a virus like influenza B spreads, we all can help prevent or slow down the infection rate.  Thank you for listening.

References: 

1. Influenza Signs and Symptoms and the Role of Laboratory Diagnostics | CDC. (2020). Cdc.gov. Retrieved 7 April 2020, from https://www.cdc.gov/flu/professionals/diagnosis/labrolesprocedures.htm#symptoms
2. Taubenberger, J. K., Hultin, J. V., & Morens, D. M. (2007). Discovery and characterization of the 1918 pandemic influenza virus in historical context. Antiviral therapy, 12(4 Pt B), 581–591.
3. The A, B, and C of influenza virus. (2020). Virology.ws. Retrieved 7 April 2020, from https://www.virology.ws/2009/09/22/the-a-b-and-c-of-influenza-virus/
4. Imai, M., Watanabe, S., Ninomiya, A., Obuchi, M., & Odagiri, T. (2004). Influenza B virus BM2 protein is a crucial component for incorporation of viral ribonucleoprotein complex into virions during virus assembly. Journal of virology, 78(20), 11007–11015. https://doi.org/10.1128/JVI.78.20.11007-11015.2004
5. Ronald L. Schnaar, in Advances in Carbohydrate Chemistry and Biochemistry, 2019

6.     Types of Influenza Viruses. (2019). Centers for Disease Control and Prevention. Retrieved 10 April 2020, from https://www.cdc.gov/flu/about/viruses/types.htm

Genomics Revolution

Benjamin Blake Erman and Ciza Sadoke

Episode 41: Influenza Virus Type A

Script:

Hello and welcome to Genomics Revolution. Today’s episode is hosted by me, Blake Erman and my partner, Ciza Sadoke, which we’ll hear from later on in the podcast. We are from Brad Goodner’s 2020 Hiram College Genetics course and today we will be focusing on the virus Influenza Type A. This virus causes Influenzae which can give you the symptoms of; a fever, chills, headaches,muscle aches, feeling tired and weak, sneezing, stuffy or runny nose, sore throat and cough (healthdirect, 2018). This disease has been thought to be around in humans for about 6000 years although the first instance of influenza symptoms were recorded around 2400 years ago. Despite this long period of time Influenza wasn’t truly discovered until 1918. This disease was discovered not from the study in humans but through studies of animal diseases by veterinarian J.S. Koen. Koen noticed the close similarities of the disease in pigs that he was working on compared to the then ongoing “Spanish” influenza pandemic of 1918. However, the Spanish influenza pandemic has not been the only influenza type A caused pandemic. According to a review article by Susan Baigent and John McCauley Influenza Type A has caused six pandemics throughout both the 19th and 20th centuries (Baigent, 2003). These pandemics have resulted from the introduction of genes from an animal-derived virus being put into the genetic background of a currently circulating human virus by the process of reassortment (Baigent, 2003). Due to reassortment being a highly developed ability of the disease and the disease causing high mortality throughout time in both humans and animals it is important to understand it to prevent its spread.

It wasn’t until 1933 through the diligent work of researchers Christopher Andrews, Patrick Laidrow, and Wilson Smith that the first human influenza virus was discovered (Kuszewski, 2000). Through their work a vaccine was made and the influenza virus was found to belong to the Orthomyxoviridae family. This family can be divided into two genera, the first includes both influenza A and B viruses while the second the influenza C virus (Kuszewski, 2000). For today, we will be focusing on this first genera, the one including influenza A. The type A virus has many subtypes that are distinguished by the antigenic properties of surface glycoproteins of the virus (Kuszewski, 2000). These glycoproteins are haemagglutinin (HA) and neuraminidase (NA) and they have 15 and nine different types respectively (Kuszewski, 2000). These multiple different types add to influenza type A’s complexity and is why it is a recurring disease. Most of the pandemics previously mentioned were caused by different compositions of this virus such as H1N1 or H2N2. And now to pass it off to my partner.

Hello my name is Ciza Sadoke and I will be finishing the rest of today’s podcast. Picking up where my partner left off, Influenza type A’s genome consists of eight negative sense single-stranded RNA molecules and they can range in size from 890 nucleotides to 2341 nucleotides (McCauley, 1983). These eight RNA molecules total up to about 14,000 nucleotides in length (Virology, 2009) and encode for eleven proteins (Samji, 2009). There are two ways that the influenza type A virus can change, and these changes are continuously happening at random in the genome. One of the ways the influenza virus can change is through Antigenic drift. These are small changes in the genes of the influenza virus that can lead to changes in the surface proteins. This means that they get recognized by the immune system and are capable of triggering an immune response. The genetic drift of influenza virus genomic sequences occurs through the combined effects of sequence alterations introduced by a low-fidelity polymerase and the varying selective pressures experienced as the virus migrates through different host environments (Kim, 2018). 

The other way the influenza type A virus can change is through antigenic shift. Antigenic shift occurs when there is an abrupt major change in the influenza A virus. This can result in new HA and NA proteins in the influenza viruses that can infect humans. These shifts can result in different influenza A subtypes in humans. One way shift can happen is when an influenza virus from an animal population gains the ability to infect humans. When a virus is produced that can infect human cells and it has new subtypes of these proteins. The people population will now have to little no protection against it, and therefore the virus will be rapidly spread throughout population. This antigenic shift process is responsible for three major influenza pandemics in the 20th century, including the Spanish flu in 1918, which killed 3% of the worlds entire population at the time (Taubenberger,2006). Also, due to the segmented genome of influenza type A, recombination can occur quite frequently and make a form of the virus that populations have no immunity against (McCauley, 1983). Even current human influenza virus vaccines are only protective against currently circulating strains and close variants of the virus (Baigent, 2003). These vaccines contain inactivated mixture of types A and B strains and this would not have been possible without its sequenced genome. This is all that we have time for today. Thank you for listening to today’s episode of Genomics Revolution. We hope you have enjoyed and have a good day!

References:

Baigent, S. J., & Mccauley, J. W. (2003). Influenza type A in humans, mammals and birds: Determinants of virus virulence, host-range and interspecies transmission. BioEssays, 25(7), 657–671. doi: 10.1002/bies.10303

Influenza A (flu). (May 2018). Retrieved April 5, 2020, from https://www.healthdirect.gov.au/influenza-a-flu

Influenza Type A Viruses. (2017, April 19). Retrieved April 5, 2020, from https://www.cdc.gov/flu/avianflu/influenza-a-virus-subtypes.htm

Kim, H., Webster, R., & Webby, R. (2018, March 01). Influenza Virus: Dealing with a Drifting and Shifting Pathogen. Retrieved April 10, 2020, fromhttps://www.liebertpub.com/doi/abs/10.1089/vim.2017.0141?rfr_dat=cr_pub

Kuszewski, K., & Brydak, L. (2000). The epidemiology and history of influenza. Biomedicine & Pharmacotherapy, 54(4), 188–195. doi: 10.1016/s0753-3322(00)89025-3

McCauley, J. W., & Mahy, B. W. J. (1983). Structure and function of the influenza virus genome. Biochemical Journal, 211(2), 281–294. doi: 10.1042/bj2110281

Noronha, J., Liu, M., Squires, R., Pickett, B., Hale, B., Air, G., . . . Scheuermann, R. (2012, May 15). Influenza Virus Sequence Feature Variant Type Analysis: Evidence of a Role for NS1 in Influenza Virus Host Range Restriction. https://jvi.asm.org/content/86/10/5857

Samji T. (2009). Influenza A: understanding the viral life cycle. The Yale journal of biology and medicine, 82(4), 153–159.

Taubenberger, J., & Morens, D. (2006, January). 1918 Influenza: The mother of all pandemics. Retrieved April 10, 2020, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291398/

“Influenza Virus RNA Genome.” Virology Blog Header Image, 16 Dec. 2009, www.virology.ws/2009/05/01/influenza-virus-rna-genome/.

Genomics Revolution Podcast

Allison Slutz & Cole Filer
Episode 40: Measles & Morbillivirus

Hi all. Welcome back to another episode of Genomics Revolution. Today you are hosted by Cole Filer and myself, Allison Slutz. We are part of the 2020 Hiram College genetics course and will be talking about the Measles morbillivirus, the virus that causes the measles.

The genus that morbillivirus is apart of, is the family Paramyxoviridae (1). The measles virus genome typically consists of 115,894 nucleotides, and encodes for 8 proteins: 6 structural (N, P, M, F, H, L) and 2 non-structural (V and C) (5). This family has enveloped viruses that have negative non-segmented single-stranded RNA genomes (1). This family also has several members that cause several issues. These are highly infectious in their nature and spread by the respiratory system (1). At the cellular level, infections from morbillivirus are initially caused by the binding of hemagglutinin glycoprotein to cellular receptors and the two receptors found in wild-type morbilliviruses are CD150 also referred to as signaling lymphocyte activation molecule F1, and the poliovirus receptor-like 4 (1).

One of the key findings that emerged from the sequenced virus genome is the number of different strains that exist, and tracking the mutation of the virus, which would allow for better development of vaccines and prevention of the spreading of measles.

Before moving forward, it’s important to understand the history of measles. The first documentation was by a Persian doctor in 9th century AD (3). Later, in 1757, a Scottish physician by the name of Francis Home demonstrated that measles are caused by a blood-borne infectious agent (3). A notable date for America is the first domestically reported case. During the time of the European immigration in 1765, the measles was first reported (3).

We should care about this virus because if we didn’t understand how it was transmitted and how to prevent it, it would kill a lot of people, and a large portion of those would be children. Measles are transmitted by coughing and sneezing, this is because the virus lives in the nose and throat of a person with this illness (2). This virus has the potential to live in the air for two hours and up to 90% of people who do not have immunity and come in contact with an infected person, will contract measles (2).

Just for the sake of reference, there are roughly 200 deaths per 100,000 cases in immunocompetent people, and around 100 cases of encephalitis per 100,000. Additionally, 1 in every 20 children that contract measles end up developing pneumonia as a complication, which happens to be the most common cause of death in young children from measles (4).

As previously stated, measles cause a significant amount of people to die, specifically children. The current vaccine used in the United States is the measles, mumps, rubella, and varicella developed in 1968 by John Enders and colleagues (3). In 2014, there was an increase of death from the measles (1). This could be correlated to some individuals and groups within first world countries that don’t believe that vaccines are necessary. Viruses do not discriminate between social classes and a person’s overall wealth. This is why everyone should protect themselves with vaccines. Vaccines are the best way to prevent the measles. We hope you enjoyed this episode of Genomics Revolution on the measles. Please continue to tune in to hear our peers on other notable viral genomes that have molded our history.

Works Cited:

1. Vries RD, Duprex W, Swart RD. Morbillivirus Infections: An Introduction. 2015;7(2):699–706.

2. Transmission of Measles. 2018 Feb 5 [accessed 2020 Apr 10]. https://www.cdc.gov/measles/transmission.html

3. Measles. 2018 Feb 5 [accessed 2020 Apr 9]. https://www.cdc.gov/measles/about/history.html

4. Measles Data and Statistics. Center for Disease Control. 2019 Apr 16 [accessed 2020 Apr 9]. www.cdc.gov/measles/downloads/measlesdataandstatsslideset.pdf

5. Phan MVT, Schapendonk CME, Munnink BBO, Koopmans MPG, Swart RLD, Cotten M. Complete Genome Sequences of Six Measles Virus Strains. Genome Announcements. 2018 [accessed 2020 Apr 9];6(13). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5876482/. doi:10.1128/genomea.00184-18

Cool Audio That Goes with This Episode:

​“I’m a Virus.” Sciencemusicvideos, 2012. www.youtube.com/watch?v=kYf_Sl8W3qY&t=2s

​“D.J. Tools Let’s Get Ready to Rumble Sound Effect.” All Sounds, 2015. www.youtube.com/watch?v=Ozol5AYYg5c

​Paxton, Tom. “I’ve got the measles.” I’ve got a yo-yo., Pax Records, 1997. www.youtube.com/watch?v=iyJ9Tvv8aWw

Zach Walker & Alainna Conroy

Virus: Varicella zoster virus

Disease: Chickenpox/ Shingles

Welcome to today’s episode of Genomics Revolution. I am Zach Walker and am here with Alainna Conroy and we will be discussing the varicella zoster virus. We will be referring to this as the VZV.  

BACKGROUND/ DISCOVERY:

In 1888, Von Bokay first observed that the VZV was related herpes zoster virus or shingles when children contracted VZV from adults who had shingles. Then in 1954, Thomas Weller took cell cultures from VZV lesions to scientifically distinguish VZV from shingles. After this in the 1970s, Japan developed the Oka strain of the varicella vaccine.

WHY WE CARE:

VZV causes chickenpox or shingles. Chicken pox results from initial infection of the VZV and occurs in children. The VZV can remain silenced in individuals and become activated later in life resulting in shingles. 

GENOME: 

VZV is a member of the varicellovirus genus and belongs to the alpha-herpesvirus family. The VZV genome has at least 70 genes, most of them homologs in herpes simplex virus. 

In 1986, the complete sequence of the VZV genome was determined by Davison and Scott. They determined the genome is variable in size, but the sequence they looked at was 124, 884 base pairs and contained 70 genes between 2 strands of DNA. The VZV genome encodes at least 71 unique proteins. The sequence is linear with a single unpaired nucleotide on each end. These will pair together and become circular in cells that are infected with the virus. 

FINDINGS FROM SEQUENCING

After sequencing the VZV genome, Davidson and Scott determined that there are a lot fewer repeats among the sequence compared to HSV-1 and the places with repeats are unrelated to HSV-1. The research describe these repeats as accumulated parasitic sequences that possibly happen through recombination, in regions that they do not cause a selective disadvantage. This affects the size of some of the encoded proteins and could have a role in different functions of these genes. 

By looking at the sequence and determining the gene layout, Davidson and Scott were able to determine that both the VZV and HSV-1 have similar gene layouts. Many of the genes encode similar proteins with specific properties. Research reports that there are also a limited amount of regions with significant differences. This indicates that the proteins are highly conserved and can be determined that the functions of VZV and HSV-1 are very similar. 

In a study done by Argaw et al, they were able to determine distinguishing parts in the nucleotide sequence between the originally sequenced VZV and the VZV Oka vaccine strain. They looked at about 34,000 from the 3’ end, they were able to see numerous changes that they describe as “nonconservative amino acid substitutions in coding sequences for virus gene products” (1154). The biggest change occurred in ORF62 where a glycine was substituted for an arginine leading to a cleave site. The study reports that mutations in ORF62 may factor into attenuation of the Oka vaccine strain. There is also a nucleotide insertions that allow a distinction.

Another finding by Lebrun et al is that ORF9p binds to the adaptor protein complex 1 also known as AP-1. AP-1 is involved in the intra-cellular transport and moving proteins between endosomes and the trans-Golgi network. With this interaction between ORF9p and AP-1 it allows the secondary envelopment of VZV. However, in the same study conducted by Lebrun et al they were able to determine that leucine 231 is conserved among alphahepresviruses and was critical in interaction between ORF9p and AP-1. To help show this,  they mutated leucine 231 to alanine in ORF9p and found that by mutating leucine 231 to alanine it strongly impaired the viral growth of VZV.

This ends today’s episode of Genomics Revolution, thank you for your time and we hope you were able to learn something new!

Works Cited:
Argaw, T., Cohen, J. I., Klutch, M., Lekstrom, K., Yoshikawa, T., Asano, Y., Krause, P. R. (2000) Nucleotide sequences that distinguish Oka vaccine from parental Oka and other Varicella-Zoster Virus isolates. The Journal of Infections Diseases, 181, 1153-1157. 

Centers for Disease Control and Prevention, “Varicella” wonder.cdc.gov/wonder/prevguid/p0000108/p0000108.asp

Cohen, J. I., The Varicella-Zoster Virus Genome. Curr Top Microbiol Immunol., 342, 1-14. 

Davison, A. J., Scott J. E. (1986). The complete DNA sequence of Varicella-Zoster Virus. J. Gen. Virol. 67, 1759-1816. 

Lebrun, M., Lambert, J., Riva, L., Thelen, N., Rambout, X., Blondeau, C., Thiry, M., Snoeck, R., Twizere, JC., Dequiedt, F., Andrei, G., Sadzot-Delvaux, C. (2018) Varicella-Zoster Virus ORF9p Binding to Cellular Adaptor Protein Complex 1 Is Important for Viral Infectivity. J Virol. 92, 1-22