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Journal of Virology, January 2002, p. 707-716, Vol. 76, No. 2
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.2.707-716.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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

Tuofu Zhu,1,2* David Muthui,1 Sarah Holte,3 David Nickle,2 Feng Feng,1 Scott Brodie,1 Yon Hwangbo,1 James I. Mullins,1,2 and Lawrence Corey1,2,4

Departments of Laboratory Medicine,1 Microbiology, University of Washington School of Medicine, Seattle, Washington 98195,2 Programs in Biostatistics,3 Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, Washington 981044

Received 23 May 2001/ Accepted 28 September 2001

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.

* Corresponding author. Mailing address: Department of Laboratory Medicine, University of Washington, P.O. Box 358070, Room 362, 960 Republican St., Seattle, WA 98195-8070. Phone: (206) 732-6079. Fax: (206) 732-6055. Email: tzhu{at}u.washington.edu.

Journal of Virology, January 2002, p. 707-716, Vol. 76, No. 2
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.2.707-716.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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