HIV & AIDS - The Killer That Robs Us of Our Immune Defenses

Genomics Revolution

Genomics Revolution

Guest Hosts: Emily Harris & Tim Murton

Episode 48: HIV & AIDS

Script:

Welcome to Genomics Revolution! This is Emily Harris and this is Tim Murton. We are from the 2020 Hiram College Genetics course, and we are hosting this episode on the genome of Human Immunodeficiency Virus, or HIV. HIV targets a host’s immune system and causes it to fail. This complication is referred to as HIV infection, and can eventually develop into acquired immunodeficiency syndrome, or AIDS, which is the most advanced stage of HIV infection (1).

This virus is in the genus lentivirus, the family of Retrovirdae, and the subfamily Orthoretrovirinae (1). HIV is typically divided into two types, HIV-1 and HIV-2, and each type can be subdivided into several smaller groups based on differences in viral antigens, and from where each strain evolved (3). HIV was recognized on a wide scale during an outbreak in the 1980s, but was actually first discovered in humans between 1920 and 1940 (1). After years of studying the virus, it was discovered that it is spread through contact with infected bodily fluids like blood, semen, breast milk, or several others. It was also discovered that the virus was very similar, genetically, to simian immunodeficiency-deficiency virus, or SIV, which is a non-human primate immunodeficiency virus (1). HIV-1 appears to have evolved from SIV strains in chimpanzees in Central Africa, and HIV-2 likely evolved from a strain in West African mangabeys (1). So it is believed that the virus was transmitted to humans when these primates were hunted for meat and their infected blood was ingested. The virus then mutated and evolved in humans into HIV (3).

Now let’s talk about the HIV genome. The genome of this virus consists of two single stranded RNA molecules and is roughly 9,200 bases in size (2). After sequencing the genome, it was found that it contains 9 genes and encodes 15 viral proteins, which is relatively small when we consider how powerful of a virus it is (3). HIV is also classified as an enveloped retrovirus (1). This means the virus uses a special enzyme called reverse transcriptase, which turns its RNA into DNA, then uses that DNA to infect a host (1). They literally insert a copy of their own genome into a host’s genome!

So this virus works in a very intelligent way making treatment for infection extremely difficult, especially before the virus was understood. This is why it was so important to sequence the HIV genome. By learning more about the genetic makeup of HIV, it became easier to understand how the virus operates, how it evolves and what it evolved from, how to prevent possible outbreaks, and what types of treatment may work. Sequencing the genome even opened the door to possible gene therapy that can be used to treat or hopefully even cure the disease someday!

Sequencing the HIV genome told us a lot about the virus, so let’s highlight a few of the key findings. Sequencing the genome is how we found out that HIV is closely related to SIV (5). This information was crucial because then we were able to use our understanding of SIV to help come up with a better treatment for HIV.

Another finding was that there are subtypes of HIV-1 such as the CG-0018a-01 HIV-1 genome (7). This subtype-L was found in the Democratic Republic of the Congo. The research showed that this subtype-L was found to be transmitting in the DRC and that there could be more strains circulating (7). Knowing this was extremely important because it shows the dangers of mutations, and how easily the virus can evolve and create new strains. This let scientists know to look out for new strains of HIV that could be more easily transmitted and harder to combat than the original strain.

Sequencing the HIV genome also showed us that HIV-1 genetic material is damaged by hypermutation (6). G-to-A hypermutation, for example, damages the virus by producing abnormal amounts of transitions from guanine to adenine. These mutations are thought to be caused by HIV’s reverse transcriptase enzyme, which has the ability to hypermutate in the presence of unbalanced nucleotide pools during the cell cycle (6). This is important because it shows that the virus has a weakness that is possibly being caused by a host mechanism that can decrease virus replication. This finding implies that if we can promote hypermutation states in HIV, we may be able to induce non-reversible mutagenesis of the viral DNA. This strategy may pave the way to discovering a cure for HIV! Thanks for listening!

References:

[1] Arbeitskreis Blut, Untergruppe ‘Bewertung Blut- assoziierter Krankheitserreger’: Human

immuno- deficiency virus (HIV). Transfus Med Hemother 2004;31:102–114.

[2] Feinberg Mark B, Greene Warner C (1992). "Molecular Insights into human immunodeficiency virus type1 pathogenesis". Current Opinion in Immunology. 4 (4): 466–474. doi:10.1016/s0952-7915(06)80041-5. PMID 1356348.

[3] Li G, Piampongsant S, Faria NR, Voet A, Pineda-Peña AC, Khouri R, Lemey P, Vandamme AM,

Theys K (February 2015). "An integrated map of HIV genome-wide variation from a population

perspective". Retrovirology. 12 (1): 18. doi:10.1186/s12977-015-0148-6. PMC 4358901. PMID 25808207.

[4] German Advisory Committee Blood (Arbeitskreis Blut), Subgroup ‘Assessment of Pathogens Transmissible by Blood’ (2016). Human Immunodeficiency Virus (HIV). Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie, 43(3), 203–222.

[5] Janini, M., Rogers, M., Birx, D. R., & McCutchan, F. E. (2001). Human immunodeficiency virus type 1 DNA sequences genetically damaged by hypermutation are often abundant in patient peripheral blood mononuclear cells and may be generated during near-simultaneous infection and activation of CD4(+) T cells. Journal of virology, 75(17), 7973–7986.

[6] Williams, K. C., & Burdo, T. H. (2009). HIV and SIV infection: the role of cellular restriction and immune responses in viral replication and pathogenesis. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica, 117(5-6), 400–412.

[7] Yamaguchi, Julie BS; Vallari, Ana MS; McArthur, Carole MD, PhD; Sthreshley, Larry PhD; Cloherty, Gavin A. PhD; Berg, Michael G. PhD; Rodgers, Mary A. PhD. (2020) Complete Genome Sequence of CG-0018a-01 Establishes HIV-1 Subtype L. JAIDS Journal of Acquired Immune Deficiency Syndromes: Volume 83 - Issue 3 - p 319-322