title: Genotypic Prediction of Co-receptor Tropism of HIV-1 Subtypes A and C.
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.
authors.affiliation: Department of Bioinformatics, Straubing Center of Science, University of Applied Sciences Weihenstephan-Triesdorf, Straubing, Germany.
authors.forename: Mona
authors.initials: M
authors.lastname: Riemenschneider
authors.affiliation: Center for Biomedical Research, Burnet Institute, Melbourne, Australia.
authors.forename: Kieran Y
authors.initials: KY
authors.lastname: Cashin
authors.affiliation: Department of Bioinformatics, University of Duisburg-Essen, Essen, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Budeus
authors.affiliation: Institute of Virology, University of Cologne, Cologne, Germany.
authors.forename: Saleta
authors.initials: S
authors.lastname: Sierra
authors.affiliation: Viral Hepatitis and Immunobiology Lab, University Hospital Aachen, Aachen, Germany.
authors.forename: Elham
authors.initials: E
authors.lastname: Shirvani-Dastgerdi
authors.affiliation: Iranian Research Center of HIV /AIDS, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Bayanolhagh
authors.affiliation: Institute of Virology, University of Cologne, Cologne, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Kaiser
authors.affiliation: Center for Biomedical Research, Burnet Institute, Melbourne, Australia.|School of Applied Sciences, and Program in Metabolism, Exercise and Disease, Health Initiatives Research Institute, RMIT University, Melbourne, Australia.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Gorry
authors.affiliation: Department of Bioinformatics, Straubing Center of Science, University of Applied Sciences Weihenstephan-Triesdorf, Straubing, Germany.|Wissenschaftszentrum Weihenstephan, Technische Universität München, Freising, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Heider
mesh_terms: D019295:Computational Biology / Q000379:methods*; D005838:Genotype; D060005:Genotyping Techniques / Q000379:methods*; D015699:HIV Envelope Protein gp120 / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D056189:Viral Tropism
chemical_list: D015699:HIV Envelope Protein gp120; C514793:gp120 protein, Human immunodeficiency virus 1