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CD4 is the predominant cell membrane protein that binds human immunodeficiency virus type 1 (HIV-1) gp120 and facilitates HIV-1 infection, but other membrane-associated molecules may be involved in determining HIV-1 cellular infection. Our prior work had suggested that CD44, the transmembrane receptor for hyaluronan, might play a role in the infection of mononuclear phagocytes with HIV-1. In the present work, we have used cells of the CD4-positive, CD44-negative human T-lymphoblast cell line Jurkat to study the role of CD44 in HIV-1 infection and tropism. Cells were transfected with cDNA for the standard (S, or hematopoietic) CD44 isoform CD44S or the epithelial isoform CD44E. The resultant lines expressed appropriate CD44S or CD44E mRNA and protein. While the parent Jurkat cells, those transfected with vector alone, and those transfected with CD44E could be productively infected with only the lymphocytotropic strain HIV-1-LAI, cells transfected with CD44S were rendered susceptible to productive infection with the monocytotropic strains HIV-1-BaL and HIV-1-ADA. Also, CD44S-transfected cells displayed higher levels of infection with HIV-1-LAI than did the other transfected Jurkat cells. The transfected cell line cells all had comparable growth rates and expressed similar levels of the membrane antigens CD4, CD7, major histocompatibility complex (MHC) class I, MHC class II, and CD11a, while levels of CD3 were slightly higher in cells transfected with vector alone and in one of the clones transfected with CD44S. Hyaluronan binding was increased in cells transfected with either CD44S or CD44E. Mouse NIH 3T3 fibroblasts transfected with human CD4, human CD44S, or both human CD4 and CD44S displayed the appropriate antigens, but they could not be productively infected with lymphocytotropic or monocytotropic strains of HIV-1. The results indicate that in human leukocytes, CD44S is an important determinant of HIV-1 productive infection and may be involved in viral cellular tropism.

Neopterin is a pteridine produced by human mononuclear phagocytes, usually in response to interferon-gamma (IFN-gamma) stimulation. Increasing serum levels of neopterin correlate with clinical progression to AIDS in HIV-infected people, but the factors that contribute to these elevated levels are not established. We performed in vitro experiments to investigate the possibility that HIV-1 infection of mononuclear phagocytes directly induces enhanced neopterin production. We found that HIV-1-infected monocytes and peritoneal macrophages produced neopterin in quantities similar to amounts produced by uninfected cells. The HIV-infected cells responded to stimulation with IFN-gamma as well as uninfected cells, with a 6- to 12-fold increase in neopterin production. We conclude that elevated serum levels of neopterin in HIV-infected individuals are not caused by HIV-1 infection of mononuclear phagocytes but may be a result of the normal response to mononuclear phagocytes to increased levels of IFN-gamma.

Human immunodeficiency virus type 1 (HIV-1) infects mononuclear phagocytes, cells that may serve as a reservoir for viral persistence. Infection with HIV-1 leads to progressive compromise of the immune system, resulting in infections with opportunistic pathogens and eventual death. Experiments were designed to determine if in vitro HIV-1 infection of mononuclear phagocytes would diminish their oxidative capabilities, thus decreasing their antimicrobial effectiveness. Blood monocytes and peritoneal macrophages were obtained from uninfected donors and inoculated with a monocytotropic strain of HIV-1. Hydrogen peroxide production and reduction of nitroblue tetrazolium were measured after acute stimulation of cells with PMA or a phagocytic stimulus. Despite vigorous virus production, no difference was seen in oxidative burst between uninfected cells and infected cells or between monocyte-derived and peritoneal macrophages. In conclusion, reduced antimicrobial activity of HIV-infected mononuclear phagocytes is probably not secondary to decreased ability to generate reactive oxygen species.