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Unveiling the Intricacies of HIV-1's gp120 and gp41 Glycoprotein Envelope Gene Evolution through a .

Annie Tran, MS, Pharmaceutical Science, (tranan85@students.rowan.edu), Department of Molecular & Cellular Biosciences, College of Science and Mathematics, Rowan University, Glassboro, New Jersey 08028, United States. Nicholas Paradis, PhD, Pharmaceutical Science, (paradi84@rowan.edu), Department of Molecular & Cellular Biosciences, College of Science and Mathematics, Rowan University, Glassboro, New Jersey 08028, United States. Chun Wu, Associate Professor, (wuc@rowan.edu), Department of Molecular & Cellular Biosciences, College of Science and Mathematics, Rowan University, Glassboro, New Jersey 08028, United States.


Poster # 27


Human immunodeficiency virus type 1 (HIV-1) is a single-stranded RNA retroviruscontaining 9,181 nucleotides. Vaccine approval for HIV-1 is challenging due to the high mutation rate that allows the virus to evade and adapt to the immune system and antivirals. The major conserved glycoprotein envelope genes gp120 and gp41, which are critical for mediating virus entry into the host cell, are currently being assessed as targets for broadly neutralizing antibodies (bNAbs). Therefore, understanding the true molecular evolution of these genes can significantly aid in optimizing HIV-1 bNAbs and potentially vaccine design. The current understanding for the molecular evolution of HIV-1 is believed to follow Kimura's neutral theory (KNT), in which mutations are neutral and do not affect the virus' fitness. Yet, KNT cannot exclusively explain the high adaptability of this virus, suggesting it may undergo Darwin's Natural Selectionist Theory (ST). But can either theory explain the evolution of this virus? Our recently proposed Near neutral balanced selection theory (NNBST) is a hybrid theory combining ST, KNT and Ohta Nearly-Neutral Theory (ONNT) to explain the true molecular evolution of SARS-CoV-2. The molecular evolution of HIV-1 may also follow NNBST. By utilizing the reference sequenceof the complete genome of HIV-1, the relative substitution rate to mutation rate(c/µ) of each of the nucleotide/amino acid sites can be calculated. Additionally, the number of nonsynonymous substitutions (Ka, mutations change in protein sequence) and synonymous substitutions (Ks, mutations do not change in protein sequence) are determined. Through calculating c/µ and Ka/Ks of the reference sequence, the new proposed theory ofNNBST (Near neutral balanced selection theory) may exhibit a L-shape distribution graph to prove its true molecular evolution of HIV-1.

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