Pavlakis GN, Valentin A, Patenaude D; International Conference on AIDS.
Int Conf AIDS. 2000 Jul 9-14; 13: abstract no. TuPeA3103.
G.N. Pavlakis, National Cancer Institute, Sultan Street, Blg 535 Room 210, NCIFCRDC Frederick, MD 21702, United States, Tel.: +1 301 846 1474, Fax: +1 301 846 6368, E-mail: pavlakis@ncifcrf.gov
Background: Impairment of natural immunity, including decreased cytotoxic activity by natural killer (NK) cells, is a common feature of HIV-1 infected individuals. To identify the reasons for these defects, we have examined the expression of HIV receptors and susceptibility to infection of primary human NK cells. Methods: Cellular markers on cultured and uncultured PBMC were studied by three color flow cytometry. Positive selection of NK cells and other subpopulations was performed by antibody-coated magnetic beads. Molecular clones of HIV tagged by GFP were used to identify and quantitate the infected cells. HIV infection was monitored by p24 assays and by GFP production. Results: We have found that a subset of uncultured primary CD56+CD3- (NK) cells express CD4, CCR5 and CXCR4. Infection studies with GFP-tagged HIV-1 molecular clones demonstrate that isolated NK cells can be infected by either R5 or X4 restricted HIV-1 strains, as judged by GFP and p24 production. HIV-1 infection of PBMC results in depletion of CD3+T-lymphocytes and concomitant expansion of CD56+ cells, which become very important to maintain chronic viral infection in vitro. HIV-1 infected NK cells appear to be more resistant to the cytopathic effects of HIV as judged by the longer half-life of the infected CD56+ cells compared to the T-lymphocytes in the same sample. In HIV infected patients we have found expansion of CD56+ cells with specific depletion of the CD56+CD4+ subset, suggesting infection of NK cells in vivo. Conclusions: NK cells can be targets for HIV infection. The half life of infected NK is longer than T cells. The relative resistance of NK cells to the cytopathic effect of HIV suggests that these cells may be relevant for maintenance of chronic infection. Defects in natural immunity present in HIV infected patients may be the result of direct effects of the virus on NK cells.
Publication Types:
Keywords:
- Acquired Immunodeficiency Syndrome
- Antigens, CD4
- Antigens, CD56
- Communicable Diseases
- HIV Infections
- HIV Seropositivity
- HIV-1
- Humans
- In Vitro
- Killer Cells, Natural
- Receptors, CCR5
- Receptors, CXCR4
- T-Lymphocytes
- immunology
Other ID:
UI: 102238949
From Meeting Abstracts