Compartmentalization and Clonal Amplification of HIV-1 in the Male Genital Tract Characterized Using Next-Generation Sequencing

Author:

Kariuki Samuel Mundia123,Selhorst Philippe45,Anthony Colin4,Matten David4,Abrahams Melissa-Rose4,Martin Darren P.67,Ariën Kevin K.58,Rebe Kevin910,Williamson Carolyn47,Dorfman Jeffrey R.111ORCID

Affiliation:

1. Division of Immunology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa

2. International Centre for Genetic Engineering and Biotechnology, Cape Town, South Africa

3. Department of Biological Sciences, School of Science, University of Eldoret, Eldoret, Kenya

4. Division of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa

5. Virology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium

6. Computational Biology Group, Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa

7. Insitute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa

8. Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium

9. Anova Health Institute, Cape Town, South Africa

10. Department of Medicine, Division of Infectious Diseases and HIV Medicine, University of Cape Town, Cape Town, South Africa

11. Division of Medical Virology, Department of Pathology, Stellenbosch University, Cape Town, South Africa

Abstract

Within an individual living with HIV-1, factors that restrict the movement of HIV-1 between different compartments—such as between the blood and the male genital tract—could strongly influence which viruses reach sites in the body from which they can be transmitted. Using deep sequencing, we found strong evidence of restricted HIV-1 movements between the blood and genital tract in all 10 men that we studied. We additionally found that neither the degree to which particular genetic variants of HIV-1 proliferate (in blood or genital tract) nor an individual’s history of sexually transmitted infections detectably influenced the degree to which virus movements were restricted between the blood and genital tract. Last, we show evidence that viral replication gave rise to a large clonal amplification in semen in a donor with highly compartmentalized HIV-1 populations, raising the possibility that differential selection of HIV-1 variants in the genital tract may occur.

Funder

Poliomyelitis Research Foundation

International Centre for Genetic Engineering and Biotechnology

Fonds Wetenschappelijk Onderzoek

National Research Foundation

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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