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PMID: 17151109 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Isolation and characterization of replication-competent human immunodeficiency virus type 1 from a subset of elite suppressors.

Journal of virology ·Vol. 81 ·No. 5 ·2007-03-00 ·Pages 2508-18

Blankson JN, Bailey JR, Thayil S, Yang HC, Lassen K, Lai J, Gandhi SK, Siliciano JD, Williams TM, Siliciano RF

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.

MeSH Terms
Base Sequence Cohort Studies DNA, Viral/genetics Defective Viruses/genetics,isolation & purification,physiology Genes, Viral HIV Infections/immunology,virology HIV Long-Term Survivors HIV-1/genetics,isolation & purification,physiology Humans In Vitro Techniques Molecular Sequence Data Phenotype Sequence Homology, Nucleic Acid Virus Cultivation/methods Virus Replication
Chemicals
DNA, Viral
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Blankson Joel N
Department of Medicine, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA. jblanks@jhmi.edu
Bailey Justin R
Thayil Seema
Yang Hung-Chih
Lassen Kara
Lai Jun
Gandhi Shiv K
Siliciano Janet D
Williams Thomas M
Siliciano Robert F
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.02165-06
Email
jblanks@jhmi.edu
Published
2007-03-00
Epub
2006-00-06
Pages
2508-18
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC1865922
Subset
IM
Grants
NIAID NIH HHS · K08 AI051191 · United States
NIAID NIH HHS · K08 AI 51191 · United States
Databases
GENBANK
EF363122, EF363123, EF363124, EF363125, EF363126, EF363127
External Links
PubMed source DOI: 10.1128/JVI.02165-06 PMC Full Text View journal details
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