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. HIV-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.
Highlights
The design of an effective human immunodeficiency virus type-1 (HIV-1)/acquired immunodeficiency syndrome (AIDS) vaccine is still in development and its progress is debated [1]
We generated datasets from Protein databank (PDB) of known structures produced by X-ray crystallography for gp120 and gp41 shown in Tables 1 and 2, respectively
As of 12-31-2010, there were approximately 14,925 gp120 and 14,472 gp41 sequences in the Los Alamos National Laboratories (LANL) database for clades A-K
Summary
The design of an effective HIV-1/AIDS vaccine is still in development and its progress is debated [1]. BIOINFORMATION open access inter-subunit interactions, inner (core)-outer (solvent) molecular interactions, receptor and co-receptor attachment, fusion required for viral entry, and antibody and CTL immunity Another key issue is that AA sequences may vary widely within and among HIV-1 clades, there may be immunologically conserved three-dimensional structures that provide foci for improved vaccine development [6,7,8,9,10]. Concomitant with the sequence variability ceiling, variability tended to occur at restricted locations in HIV-1 proteins including in ENV Entropy studies for both clades B and C demonstrated that increased entropy occurred at AA sites with less constraint, and low entropy at sites with greater constraint. The mean distribution show that most residues in gp120 and gp are solvent exposed
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