CCR5- and CXCR4-Tropic Subtype C Human Immunodeficiency Virus Type 1 Isolates Have a Lower Level of Pathogenic Fitness than Other Dominant Group M Subtypes: Implications for the Epidemic
- 1 June 2009
- journal article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 83 (11), 5592-5605
- https://doi.org/10.1128/jvi.02051-08
Abstract
Human immunodeficiency virus type 1 (HIV-1) subtype C is the dominant subtype globally, due largely to the incidence of subtype C infections in sub-Saharan Africa and east Asia. We compared the relative replicative fitness (ex vivo) of the major (M) group of HIV-1 subtypes A, B, C, D, and CRF01_AE and group O isolates. To estimate pathogenic fitness, pairwise competitions were performed between CCR5-tropic (R5) or CXCR4-tropic (X4) virus isolates in peripheral blood mononuclear cells (PBMC). A general fitness order was observed among 33 HIV-1 isolates; subtype B and D HIV-1 isolates were slightly more fit than the subtype A and dramatically more fit than the 12 subtype C isolates. All group M isolates were more fit (ex vivo) than the group O isolates. To estimate ex vivo transmission fitness, a subset of primary HIV-1 isolates were examined in primary human explants from penile, cervical, and rectal tissues. Only R5 isolates and no X4 HIV-1 isolates could replicate in these tissues, whereas the spread to PM1 cells was dependent on active replication and passive virus transfer. In tissue competition experiments, subtype C isolates could compete with and, in some cases, even win over subtype A and D isolates. However, when the migratory cells from infected tissues were mixed with a susceptible cell line, the subtype C isolates were outcompeted by other subtypes, as observed in experiments with PBMC. These findings suggest that subtype C HIV-1 isolates might have equal transmission fitness but reduced pathogenic fitness relative to other group M HIV-1 isolates.Keywords
This publication has 61 references indexed in Scilit:
- Elite Suppressor–Derived HIV-1 Envelope Glycoproteins Exhibit Reduced Entry Efficiency and KineticsPLoS Pathogens, 2009
- Temporal and Spatial Dynamics of Human Immunodeficiency Virus Type 1 Circulating Recombinant Forms 08_BC and 07_BC in AsiaJournal of Virology, 2008
- HLA Class I-Driven Evolution of Human Immunodeficiency Virus Type 1 Subtype C Proteome: Immune Escape and Viral LoadJournal of Virology, 2008
- Variation in HIV-1 set-point viral load: Epidemiological analysis and an evolutionary hypothesisProceedings of the National Academy of Sciences, 2007
- Molecular Umbrellas: a Novel Class of Candidate Topical Microbicides To Prevent Human Immunodeficiency Virus and Herpes Simplex Virus InfectionsJournal of Virology, 2007
- Chimpanzee Reservoirs of Pandemic and Nonpandemic HIV-1Science, 2006
- Elevated Tumor Necrosis Factor–α Activation of Human Immunodeficiency Virus Type 1 Subtype C in Southern Africa Is Associated with an NF‐κB Enhancer Gain‐of‐FunctionThe Journal of Infectious Diseases, 2000
- Tree View: An application to display phylogenetic trees on personal computersBioinformatics, 1996
- Genomic Structure of an Attenuated Quasi Species of HIV-1 from a Blood Transfusion Donor and RecipientsScience, 1995
- A game-theoretical model of parasite virulenceJournal of Theoretical Biology, 1983