Roles of Monocytes in HIV-1 Infection

NIAID/NIH RO1, PI:   Tuofu Zhu, MD

In order to enhance the efficiency of suppressive therapy, it is important to identify cells which carry out low-level HIV-1 replication and renew viral reservoirs in patients taking highly active anti-retroviral therapy (HAART).   Previous studies suggest the existence of viral sources other than resting CD4+ T cells.   While CD4+ T cells and tissue macrophages are potential viral reservoirs, the role(s) of monocytes in HIV-1 infection in vivo remain unclear.   Our recent studies indicate that despite HAART, ongoing HIV-1 replications occurs in vivo in blood monocytes.   We have also found that HIV-1 replication in monocytes is an important source of persistent HIV-1 replications among persons on HAART.   The goal of this project is to extend our current understanding of HIV-1 dynamics in monocytes/macrophages; and to define their role(s) in HIV-1 infection in the context of antiretroviral drugs.   Findings from this study will provide better understanding of productive HIV-1 infection in monocytes and macrophages in vivo .   These findings may also provide great insights in developing new therapeutic strategies which will enhance drug efficacy.

Publications:

• Zhu T , Muthui D, Holte S, Nickle D, Feng F, Brodie SJ, Hwangbo Y, Mullins JI, and Corey L. Evidence for HIV-1 Replication in vivo in CD14+ Monocytes and Its Potential Role as A Source of Virus in Patients on Potent Therapy. J. Virol. 76: 707-716, 2002.

• Zhu T. HIV-1 in Peripheral Blood Monocytes: An Underrated Virus Source. J. Antimicrob. Chemother., 50:309-311, 2002.

• Learn G, Muthui D, Brodie SJ, Zhu T , Diem K, Mullins JI, & Corey L. Virus Population Homogenization Following Acute Human Immunodeficiency Virus Type 1 Infection. J. Virol. 76: 11963-11959, 2002.

• Malhotra U, Holte S, Zhu T , Delpit E, Huntsberry C, Sette A, Shankarappa R, Maenza J, Corey L, and McElrath1 MJ. Early Induction and Maintenance of Env-Specific T-helper Cells Following Acute Human Immunodeficiency Virus Type 1 Infection, J. Virol. 77: 2663-2674, 2003.

• Zhu T . HIV-1 Genotypes in Peripheral Blood Monocytes. J. Leuko. Bio. 66: 338-344, 2000.

• Bures R, Gaitan A, Zhu T , Graziosi C, McGrath KM, Tartaglia J, Caudrelier P, El Habib R, Klein M, Lazzarin A, Stablein DM, Deers M, Corey L, Greenberg ML, Schwartz DH, Montefiori DC. Immunization with recombinant canarypox vectors expressing membrane-anchored glycoprotein 120 followed by glycoprotein 160 boosting fails to generate antibodies that neutralize R5 primary isolates of human immunodeficiency virus type 1. Aids Research and Human Retroviruses. 16(18): 2019-35, 2000.

• Zhu T , Wang N, Carr A, Nam DS, Moor-Jankowski R, Cooper DA, Ho DD. Genetic characterization of human immunodeficiency virus type 1 in blood and genital secretions: evidence for viral compartmentalization and selection during sexual transmission. Journal of Virology. 70(5): 3098-107, May 1996.

• Zhu T , Wang N, Carr A, Wolinsky S, Ho DD. Evidence for coinfection by multiple strains of human immunodeficiency virus type 1 subtype B in an acute seroconvertor. Journal of Virology. 69(2): 1324-7, Feb 1995.

• Zhu T , Mo H, Wang N, Nam DS, Cao Y, Koup RA, Ho DD. Genotypic and phenotypic characterization of HIV-1 patients with primary infection. Science. 261(5125): 1179-81, 1993.