Differential cellular distribution of HIV-1 drug resistance in vivo: evidence for infection of CD8+ T cells during HAART.
This study presents a detailed analysis of HIV-1 populations isolated from total PBMC, plasma, CD4+ T cells, CD8+ T cells, and monocytes/macrophages in 13 patients receiving HAART. Sequence analysis of the reverse transcriptase and protease genes indicated that viral strains isolated from different blood leukocytes were genetically distinct in each subject. Notably, HIV variants isolated from CD8+ T cells were distantly related to strains derived from other blood cell types, providing evidence for the strain-specific infection of CD8+ T cells in vivo. Compartmentalization of drug resistance mutations in specific blood cell types was observed in approximately 50% of patients. The prevalence of resistance mutations was higher in either CD4+ T cells or monocytes/macrophages in these subjects. However, CD8+ T cells showed markedly lower levels of viral drug resistance in these patients, indicating a lack of viral replication in this compartment. This study is the first to demonstrate the differential distribution of HIV drug resistance in different blood cell types during HAART and provides new insights into the infection of CD8+ T cells in vivo.
Potter
Simon J
SJ
Retroviral Genetics Laboratory, Center for Virus Research, Westmead Millennium Institute, Westmead Hospital and The University of Sydney, New South Wales 2145, Australia.
Dwyer
Dominic E
DE
Saksena
Nitin K
NK
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy; D023241:Antiretroviral Therapy, Highly Active; D018414:CD8-Positive T-Lymphocytes / Q000821:virology*; D002469:Cell Separation; D024882:Drug Resistance, Viral; D015497:HIV-1 / Q000145:classification / Q000187:drug effects*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D010802:Phylogeny; D014766:Viremia / Q000821:virology