Abstract The purpose of this experiment was to determine whether a host’s single nucleotide polymorphisms (SNPs) in the Vif- associated APOBEC3G Proteasomal Complex infuence his/her innate immunity to Human Immunodefciency Virus-1. The experimenters compared host DNA at specifc sites on each patient’s genome (SNPs) and the patient’s HIV- 1 disease progression. They extracted DNA from peripheral blood mononuclear cells. Then, using high-throughput microarray nano-liter plates, a polymerase chain reaction (PCR) was run. The PCR gave a signal reading which the experimenters then translated into a genotype reading. Anonymous patient data concerning each individual’s HIV progression were obtained from the National Institute of Health. The experimenters used a univariate analysis along with logistic regression to obtain a P-value, which was then corrected for multiple testing errors. A total of 5,000 patients were analyzed for each of 125 SNPs. After analysis, the experimenters found that the SNPs tested did not have a signifcant correlation with the viral set-point due to the high q-values that were above .05. Also, there was not a signifcant correlation between the SNPs tested and the patient CD4+ T-Cell slope. However, the study found an association that trended towards signifcance between HIV progression and the APOBEC3G associate SNP rs3736685. Introduction Human immunodefciency virus (HIV) is a retrovirus that is prevalent throughout much of the world. HIV affects 33.3 million people worldwide and is related to substance abuse and poverty in an area 1,2 . As with all viruses, HIV replicates intracellularly. It predominantly uses CD4+ T-helper cells to replicate. Upon antigen presentation by major histocompatibility complex (MHC) class I, CD8+ cytotoxic lymphocytes initiate apoptosis of the infected cell. However, CD4+ T-cells are reduced in HIV infection, mitigating helper T-cell response. Consequently, infection with HIV is characterized by a decrease in CD4+ T cell count. As T-helper cells play a vital role in acquired immunity, infection with HIV results in a compromised immune system. There are two distinct types of the virus, aptly named HIV- 1 and HIV-2. HIV-1 is most closely related to viruses found in gorillas and chimpanzees. There is also regional variation amongst the subgroup M which is primarily due to the many genome Associations between HIV Susceptibility and Mutations in the Vif-associated APOBEC3G Proteasomal Complex Kevin Emancipator 1 *, Jack Michuda 1 *, and Sudhir Penugonda 2 ** Student 1 : The Illinois Math and Science Academy, 1500 Sullivan Road, Aurora, Illinois Mentor 2 : Northwestern University-Feinberg School of Medicine, 645 N Michigan Avenue, Suite 900 *These authors contributed equally **Corresponding author: spenugonda@gmail.com INTERNSHIP ARTICLE mutations of the HIV virus. Other subgroups of HIV-1 include group O, which refers to outliers, and group N, which refers to non-M and non-O subgroups. Furthermore, subgroup P refers to a recently analyzed HIV sequence unlike any other HIV virus that bears a stronger resemblance to simian immunodefciency virus in gorillas than that which is in infected chimpanzees. HIV-2 is far less pathogenic and rarely observed outside of Africa. It is also categorized into several regional subgroups. The study, and all references to HIV, will be concerning HIV-1 group M. As with many viruses, the HIV genome is fairly simple. The production of three structural and six accessory proteins is encoded within the genome. The six accessory proteins are VPU, REV, TAT, NEF, VPR, and VIF. VIF, or viral infectivity factor plays a role in the pathogenesis of the HIV virus by degrading the enzyme APOBEC3G by ubiqutination 3 . This process is relevant to the study and will be discussed in further detail. HIV enters a CD4+ T cell by binding to CD4+ protein on the surface of the cell. The virus then enters the cell. After undergoing reverse transcriptase, newly formed HIV DNA is transported into the cell nucleus and integrates into host DNA. The integrated DNA services as a template for further viral replication, sometimes preceded by a prolonged latency. Protease acts as a catalyst to help the formation of new viruses. After replication, new viruses bud off infected cells into the body. Apolipoprotein B mRNA-editing, enzyme-catalytic, polypeptide-like 3G (APOBEC3G) is a human enzyme that is part of a family that plays a role in innate viral immunity. APOBEC3G is known to exert antiretroviral immune activity. There are several mechanisms by which APOBEC3G is able to inhibit retrovirus reproduction. By causing deoxyctidine to deoxyuridine mutations in the HIV genome, the enzyme interferes with reverse transcription4. Furthermore, it is proposed that a nucleophilic attack causes cytidine deamination 4 . Deamination results in hypermutations G to A in the viral genome and ultimately resulting in an inability to replicate. Viral infectivity factor (Vif) is a gene that encodes for the VIF protein. This protein increases the pathogenesis of the HIV virus. The VIF protein interferes with host mediated anti-viral defense. Specifcally, it neutralizes APOBEC3G, an anti-viral enzyme. VIF inhibits the protein from entering the virion. Furthermore, by binding to APOBEC3G, proteolysis by ubiquitination is initiated, rendering the enzyme ineffective. VIF targets APOBEC3G degradation by removing Cullin5 E3 ubiquitin ligase 5 . By inactivating the APOBEC3G enzyme through VIF, HIV is able