Publications & Reports

Genotypic prediction of co-receptor tropism of HIV-1 subtypes A and C.

Riemenschneider M, Cashin KY, Budeus B, Sierra S, Shirvani-Dastgerdi E, Bayanolhagh S, Kaiser R, Gorry PR, Heider D
Department of Bioinformatics, Straubing Center of Science, University of Applied Sciences Weihenstephan-Triesdorf, Straubing, Germany.

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.

This work was supported by grants from the Bavarian Research Alliance and from the Federal Ministry of Education and Research (BMBF) and the German Academic Exchange Service (DAAD) under the ATN-DAAD Joint Research Co-operation Scheme to DH. PRG is supported by an Australian Research Council (ARC) Future Fellowship. This work was supported by the German Research Foundation (DFG) and the Technische Universität München within the funding programme Open Access Publishing.

Publication

  • Journal: Scientific Reports
  • Published: 29/04/2016
  • Volume: 6
  • Pagination: 24883

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