HIV-1 envelope accessible surface and polarity: clade, blood, and brain

Abstract

The human immunodeficiency virus type-1 (HIV-1) gp160 (gp120-gp41 complex) trimer envelope (ENV) protein is a potential vaccine candidate for HIV/AIDS. HIV-1 vaccine development has been problematic and charge polarity as well as sequence variation across clades may relate to the difficulties. Further obstacles are caused by sequence variation between blood and brain-derived sequences, since the brain is a separate compartment for HIV-1 infection. We utilize a threedimensional residue measure of solvent exposure, accessible surface area (ASA), which shows that major segments of gp120 and gp41 known structures are solvent exposed across clades. We demonstrate a large percent sequence polarity for solvent exposed residues in gp120 and gp41. The range of sequence polarity varies across clades, blood, and brain from different geographical locations. Regression analysis shows that blood and brain gp120 and gp41 percent sequence polarity range correlate with mean Shannon entropy. These results point to the use of protein modifications to enhance HIV-1 ENV vaccines across multiple clades, blood, and brain. It should be noted that we do not address the issue of protein glycosylation here; however, this is an important issue for vaccine design and development.AbbreviationsHIV-1 - human immunodeficiency virus type 1, AIDS - acquired immunodeficiency syndrome, ENV - envelope, gp160 - 160,000d glycoprotein, gp120 - 120,000d glycoprotein, gp41 - 41,000d glycoprotein, LANL - Los Alamos National Laboratories, PDB - Protein Data Bank, HVTN - STEP HIV vaccine trial, AA - amino acids, MSA - multiple sequence alignment, ASA - accessible surface area, SNPs- single nucleotide polymorphisms, HAART - Highly Active Antiretroviral Therapy, CCR5 - C-C chemokine receptor type 5, CNS - central nervous system, HIVE - HIV encephalitis, P - polarity, NP - non-polarity, CTL - cytotoxic T lymphocyte, NIAID - National Institute of Allergy and Infectious Diseases.

Deciphering Novel SARS CoV-2 specific Disease Pathways from RNA Sequencing Data of COVID-19 Infected A549 Cells and Potential Therapeutics using Next Generation Knowledge Discovery Platforms

“…Cytokines are glycoproteins released upon any external stimuli and bind with speci c cell surface receptors on the plasma membrane of target cells to elicit their responses (Pushparaj, 2019) The cytokine/chemokine storm observed in the moderate to severe cases of COVID-19 is caused by a signi cant increase in the levels of an array of circulating cytokines and chemokines such as IL-6, IL-8, TNFα, CXCL-10, etc., and contribute to the poor prognosis (Vaninov, 2020) In general, the viruses develop mechanisms to avoid detection and the subsequent destruction inside the host by repurposing and copying cytokine and cytokine receptor genes. (Pushparaj, 2019;Pushparaj et al, 2007;Sowmya et al, 2011). Similarly, the COVID-19 induced cytokines and cytokine receptors, chemokines, and other speci c cytokine receptors and binding proteins to destabilize and modify the host cytokine responses and immune networks (Pushparaj et al, 2007).…”