Evidence for human immunodeficiency virus type 1 replication in vivo in CD14(+) monocytes and its potential role as a source of virus in patients on highly active antiretroviral therapy.
In vitro studies show that human immunodeficiency virus type 1 (HIV-1) does not replicate in freshly isolated monocytes unless monocytes differentiate to monocyte-derived macrophages. Similarly, HIV-1 may replicate in macrophages in vivo, whereas it is unclear whether blood monocytes are permissive to productive infection with HIV-1. We investigated HIV-1 replication in CD14(+) monocytes and resting and activated CD4(+) T cells by measuring the levels of cell-associated viral DNA and mRNA and the genetic evolution of HIV-1 in seven acutely infected patients whose plasma viremia had been <100 copies/ml for 803 to 1,544 days during highly active antiretroviral therapy (HAART). HIV-1 DNA was detected in CD14(+) monocytes as well as in activated and resting CD4(+) T cells throughout the course of study. While significant variation in the decay slopes of HIV-1 DNA was seen among individual patients, viral decay in CD14(+) monocytes was on average slower than that in activated and resting CD4(+) T cells. Measurements of HIV-1 sequence evolution and the concentrations of unspliced and multiply spliced mRNA provided evidence of ongoing HIV-1 replication, more pronounced in CD14(+) monocytes than in resting CD4(+) T cells. Phylogenetic analyses of HIV-1 sequences indicated that after prolonged HAART, viral populations related or identical to those found only in CD14(+) monocytes were seen in plasma from three of the seven patients. In the other four patients, HIV-1 sequences in plasma and the three cell populations were identical. CD14(+) monocytes appear to be one of the potential in vivo sources of HIV-1 in patients receiving HAART.
Zhu
Tuofu
T
Department of Laboratory Medicine, University of Washington School of Medicine, Seattle, Washington 98195, USA. tzhu@u.washington.edu
Muthui
David
D
Holte
Sarah
S
Nickle
David
D
Feng
Feng
F
Brodie
Scott
S
Hwangbo
Yon
Y
Mullins
James I
JI
Corey
Lawrence
L
D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000821:virology; D002455:Cell Division; D019143:Evolution, Molecular; D015967:Gene Expression Regulation, Viral; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D006207:Half-Life; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008213:Lymphocyte Activation; D008297:Male; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism / Q000821:virology*; D009928:Organ Specificity; D010802:Phylogeny; D011533:Proviruses / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology; D012367:RNA, Viral / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014771:Virion / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology; D014779:Virus Replication
D019380:Anti-HIV Agents; D015699:HIV Envelope Protein gp120; D018950:Lipopolysaccharide Receptors; D012367:RNA, Viral