Title

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

Authors

Gopichandran Sowmya^{1, 2}, Gunasagaran Shamini^{1, 2}, Sathyanarayanan Anita¹, Meena Sakharkar³, Venkat Mathura^{4, 5}, Hector Rodriguez⁶, Andrew J Levine^{7, 8}, Elyse Singer^{7, 8}, Deborah Commins^{7, 9}, Charurut Somboonwit^{10, 11}, John T Sinnott^{10, 11}, Harcharan S Sidhu², Ganapathy Rajaseger¹², Peter Natesan Pushparaj¹³, Pandajarasamme Kangueane^{1, 2}, Paul Shapshak^{11, 14}* 

Affiliation

¹Biomedical Informatics, Pondicherry 607402, India; ²Aimst University, 08100 Semeling, Malaysia; ³Graduate School of Life and Environmental Sciences, University of Tsukuba, Japan; ⁴Archer Pharmaceuticals, Sarasota, Florida, USA; ⁵Roskamp Institute, 2040 Whitfield Avenue, Sarasota, FL 34243, US; ⁶Department of Biology, University of Miami, Coral Gables, FL 33146; ⁷National Neurological AIDS Bank, UCLA School of Medicine, Westwood, CA 90095; ⁸Department of Neurology, UCLA School of Medicine, Westwood, CA 90095; ⁹Department of Neuropathology, USC Keck School of Medicine, Los Angeles, CA90089; ¹⁰Clinical Research Unit, Hillsborough Health Department, Tampa, Florida 33602; ¹¹Division of Infectious Disease and International Medicine, Tampa General Hospital, USF Health, Tampa, FL 33601; ¹²Defense Science Organization National Laboratories, Singapore; ¹³Glasgow Biomedical Research Centre, Faculty of Medicine, Univ. of Glasgow, Glasgow, UK; ¹⁴Department of Psychiatry & Behavioral Medicine, University of South Florida, College of Medicine, Tampa, FL 33613 

Email

pshapshak@gmail.com; *Corresponding author

Article Type

Hypothesis

Date

Received March 9, 2011; Accepted March 11, 2011; Published March 22, 2011

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 three-dimensional 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.  

Keywords

HIV-1, clades, blood, brain, accessible surface area, compositional polarity, Shannon entropy, gp120, gp41, gp120-gp41 complex, gp160, ENV, trimer, vaccine.

Citation

Sowmya et al. Bioinformation 6(2): 48-56 (2011)

Edited by

F Chiappelli

ISSN

0973-2063

Publisher

Biomedical Informatics

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.