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Genotypic Prediction of Co-receptor Tropism of HIV-1 Subtypes A and C.

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Riemenschneider M, Cashin KY, Budeus B, Sierra S, Shirvani-Dastgerdi E, Bayanolhagh S, Kaiser R, Gorry PR, Heider D,


Riemenschneider M, Cashin KY, Budeus B, Sierra S, Shirvani-Dastgerdi E, Bayanolhagh S, Kaiser R, Gorry PR, Heider D, (click to view)

Riemenschneider M, Cashin KY, Budeus B, Sierra S, Shirvani-Dastgerdi E, Bayanolhagh S, Kaiser R, Gorry PR, Heider D,

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Scientific reports 2016 04 296() 24883 doi 10.1038/srep24883

Abstract

Antiretroviral treatment of Human Immunodeficiency Virus type-1 (HIV-1) infections with CCR5-antagonists requires the co-receptor usage prediction of viral strains. Currently available tools are mostly designed based on subtype B strains and thus are in general not applicable to non-B subtypes. However, HIV-1 infections caused by subtype B only account for approximately 11% of infections worldwide. We evaluated the performance of several sequence-based algorithms for co-receptor usage prediction employed on subtype A V3 sequences including circulating recombinant forms (CRFs) and subtype C strains. We further analysed sequence profiles of gp120 regions of subtype A, B and C to explore functional relationships to entry phenotypes. Our analyses clearly demonstrate that state-of-the-art algorithms are not useful for predicting co-receptor tropism of subtype A and its CRFs. Sequence profile analysis of gp120 revealed molecular variability in subtype A viruses. Especially, the V2 loop region could be associated with co-receptor tropism, which might indicate a unique pattern that determines co-receptor tropism in subtype A strains compared to subtype B and C strains. Thus, our study demonstrates that there is a need for the development of novel algorithms facilitating tropism prediction of HIV-1 subtype A to improve effective antiretroviral treatment in patients.

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