André Dascal

Bluma G Brenner

Mark A Wainberg

Yudong Quan

English

PubMed

Crossref

Highly diversified multiply drug-resistant HIV-1 quasispecies in PBMCs: a case report

Abstract Background Although drug resistance is a major challenge in HIV therapy, the effect of drug resistance mutations on HIV evolution in vivo is not well understood. We have now investigated genetic heterogeneity in HIV-1 by performing drug resistance genotyping of the PR-RT regions of viruses derived from plasma and peripheral blood mononuclear cells (PBMCs) of a single patient who had failed multiple regimens of anti-retroviral therapy. Results Patterns of drug resistance mutations showed that the viral populations in PBMCs were more heterogeneous than in plasma. Extensive analysis of HIV from infected PBMCs in this patient showed that high-level diversity existed among 109 cloned PR-RT sequences and that the majority of mutations were related to drug resistance. Moreover, the PBMCs included archival species that reflected the treatment history of the patient while those in plasma were mainly related to the most recent treatment. Some of the proviral clones contained single or multiple mutations in various combinations. Approximately eighteen percent of the proviral clones derived from infected PBMCs were defective, i.e. 5.5% contained single nucleotide deletions (frameshift mutations) and 12.8% encoded in-frame stop codons (nonsense mutations). Amino acid substitutions in PR and the polymerase region of RT occurred in 12–15% of cases but were much less frequent in the RNase H region of RT, which might not have been under drug selection pressure. Conclusion Selective drug pressure can yield multiple drug-resistant quasispecies that include archival and replication-incompetent species in PBMC reservoirs.</p

Wainberg Mark A

Dascal André

Brenner Bluma G

Quan Yudong

Directory of Open Access Journals

Retrovirology

Springer - Publisher Connector

2nd, Hall CD, Robertson KR: Impact of human immunodeficiency virus (HIV) subtypes on HIV-associated neurological disease.

A: Hostspecific driving force in human immunodeficiency virus type 1 evolution in vivo.

Arts EJ, Gao Y: HIV diversity, recombination and disease progression: how does fitness &quot;fit&quot; into the puzzle? AIDS Rev

BG: Variations in reverse transcriptase and RNase H domain mutations in human immunodeficiency virus type 1 clinical isolates are associated with divergent phenotypic resistance to zidovudine. Antimicrob Agents Chemother

BH: Molecular characterization of human immunodeficiency virus type 1 cloned directly from uncultured human brain tissue: identification of replication-competent and -defective viral genomes.

DD: HIV1 dynamics in vivo: virion clearance rate, infected cell lifespan, and viral generation time. Science

Evolutionary mechanisms and population dynamics of the third variable envelope region of HIV within single hosts.

Ho DD.: The decay of the latent reservoir of replication-competent HIV-1 is inversely correlated with the extent of residual viral replication during prolonged anti-retroviral therapy. Nat Med

I: Accumulation of defective viral genomes in peripheral blood mononuclear cells of human immunodeficiency virus type 1-infected individuals.

Independent HIV replication in paired CSF and blood viral isolates during antiretroviral therapy. Neurology

King MS: Low-level viremia persists for at least 7 years in patients on suppressive antiretroviral therapy.

Merigan TC, Kovari LC.: Crystal structures of a multidrug-resistant human immunodeficiency virus type 1 protease reveal an expanded active-site cavity.

Multiple, linked human immunodeficiency virus type 1 drug resistance mutations in treatment-experienced patients are missed by standard genotype analysis.

OG: HIV evolutionary dynamics within and among hosts. AIDS Rev

Quasispecies diversity determines pathogenesis through cooperative interactions in a viral population. Nature

Redfield RR: HIV-1 proviral genotypes from the peripheral blood mononuclear cells of an infected patient are differentially represented in expressed sequences. J Acquir Immune Defic Syndr

RNA virus fitness. Rev Med Virol

S: HIV-1 isolates are rapidly evolving quasispecies: evidence for viral mixtures and preferred nucleotide substitutions. J Acquir Immune Defic Syndr

S: MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0. Mol Biol Evol

Safrit JT: Adaptive evolution of human immunodeficiency virus-type 1 during the natural course of infection. Science

Takano T: A high frequency of defective vif genes in peripheral blood mononuclear cells from HIV type 1-infected individuals. AIDS Res Hum Retroviruses

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2426714

Highly diversified multiply drug-resistant HIV-1 quasispecies in PBMCs: a case report

Abstract

Similar works

Full text

Available Versions

Crossref

Directory of Open Access Journals

Springer - Publisher Connector

Springer - Publisher Connector