Sources of HIV-1 Mutations During Infection
Engineering
BME 195 Senior Thesis
Human Immunodeficiency Virus (HIV) infections are extremely efficacious because of the multitude of mutations from known (and possibly unknown) sources involved, such as the viral HIV reverse transcriptase (RT) enzyme, and selection due to immune response and antiretroviral drug therapy. The goal of this project is to generate a neutral HIV-1 RT mutation spectrum by restricting the mutation spectrum to only premature stop codon-causing mutations (PSCMs). Given that PSCMs are deleterious, they must have occurred pre-selection; thus a mutation spectrum consisting of only PSCMs is selection-free. Assuming that the main source of non-RT mutations during viral infection is APOBEC, a family of cytidine deaminase enzymes, APOBEC-induced mutations were filtered out by utilizing certain APOBEC mutation signatures. A Python script was written for identifying PSCMs from publicly available HIV genome sequences from the Los Alamos National Laboratory HIV Database. The script ran on three HIV genome studies so far, and of the three studies, study ERP001266 had the most PSCMs. The mutation spectrum of the HIV-1 Pol gene across the three studies and the intergenic mutation spectrum of ERP001266 were both fairly even, as expected. The in vitro and in vivo HIV-1 mutation spectra do not share any noticeable patterns with each other, as expected given the effects of selection and other mutation sources.
