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

Author:

Abraha Awet1,Nankya Immaculate L.2,Gibson Richard1,Demers Korey1,Tebit Denis M.1,Johnston Elizabeth3,Katzenstein David3,Siddiqui Asna4,Herrera Carolina4,Fischetti Lucia4,Shattock Robin J.4,Arts Eric J.12

Affiliation:

1. Division of Infectious Diseases, Department of Medicine, Case Western Reserve University, Cleveland, Ohio

2. Virology Program, Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, Ohio

3. Infectious Diseases and Geographical Medicine, Department of Medicine, Stanford University, Stanford, California

4. Center for Infection, Department of Cellular and Molecular Medicine, St. George's University of London, London, United Kingdom

Abstract

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.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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