Isolation and Characterization of Replication-Competent Human Immunodeficiency Virus Type 1 from a Subset of Elite Suppressors

Author:

Blankson Joel N.1,Bailey Justin R.1,Thayil Seema1,Yang Hung-Chih1,Lassen Kara1,Lai Jun12,Gandhi Shiv K.1,Siliciano Janet D.1,Williams Thomas M.3,Siliciano Robert F.12

Affiliation:

1. Department of Medicine, Johns Hopkins University School of Medicine

2. Howard Hughes Medical Institute, Baltimore, Maryland 21205

3. Department of Pathology, University of New Mexico School of Medicine, and Tricore Reference Laboratories, Albuquerque, New Mexico 87131

Abstract

ABSTRACT Elite suppressors (ES) are untreated human immunodeficiency virus type 1 (HIV-1)-infected individuals who control viremia to levels below the limit of detection of current assays. The mechanisms involved in this control have not been fully elucidated. Several studies have demonstrated that some ES are infected with defective viruses, but it remains unclear whether others are infected with replication-competent HIV-1. To answer this question, we used a sensitive coculture assay in an attempt to isolate replication-competent virus from a cohort of 10 ES. We successfully cultured six replication-competent isolates from 4 of the 10 ES. The frequency of latently infected cells in these patients was more than a log lower than that seen in patients on highly active antiretroviral therapy with undetectable viral loads. Full-length sequencing of all six isolates revealed no large deletions in any of the genes. A few mutations and small insertions and deletions were found in some isolates, but phenotypic analysis of the affected genes suggested that their function remained intact. Furthermore, all six isolates replicated as well as standard laboratory strains in vitro. The results suggest that some ES are infected with HIV-1 isolates that are fully replication competent and that long-term immunologic control of replication-competent HIV-1 is possible.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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