Hepatitis C - Until Now, the Silent Hepatitis Epidemic

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