Partial Activation and Induction of Apoptosis in CD4+ and CD8+ T Lymphocytes by Conformationally Authentic Noninfectious Human Immunodeficiency Virus Type 1 (original) (raw)
Related papers
Journal of Medical Virology, 2006
Several potential mechanisms for viral destruction of HIV-infected cells have been described. The hypothesis was examined that if HIV were cytopathic, a positive relation between the in vivo virus production or CTL activity and infected cell death should be observed. In a regression analysis no significant relation was found between surrogate markers for in vivo virus production or the virus-specific CTL response and death rates of productively infected cells. In a subgroup of patients the hypothesis is rejected that HIV replication elicits a large (R 2 > 0.25) cytopathic effect (P < 0.05, N ¼ 36). It is concluded that HIV replication elicits little cytopathic effect in productively infected cells and that CD4 þ T lymphocytes are eroded by other mechanisms.
Journal of Virology, 2002
An important unresolved issue of AIDS pathogenesis is the mechanism of human immunodeficiency virus (HIV)-induced CD4 ؉ T-lymphocyte destruction. We show here that HIV type 1 (HIV-1) exerts a profound cytopathic effect upon peripheral blood CD4 ؉ T lymphocytes that resembles necrosis rather than apoptosis. Necrotic cytopathology was found with both laboratory-adapted strains and primary isolates of HIV-1. We carefully investigated the role of env, which has been previously implicated in HIV cytopathicity. HIV-1 stocks with equivalent infectivity were prepared from constructs with either an intact or mutated env coding region and pseudotyped with the glycoprotein of vesicular stomatitis virus (VSV-G) so that the HIV envelope was not rate-limiting for infection. Infected Jurkat T cells died whether or not env was intact; however, the expression of env accelerated death significantly. The accelerated death was blocked by protease inhibitors, indicating that it was due to reinfection by newly produced virus in env ؉ cultures. Accordingly, we found no disparity in kinetics in CD4 lo Jurkat cells. In highly infected peripheral blood T cells, profound necrosis occurred equivalently with both env ؉ and env ؊ stocks of HIV-1. We also found that HIV-1 cytopathicity was undiminished by the absence of nef. However, viral stocks made by complementation or packaging of HIV-1 genomes with the natural protein-coding sequences replaced by the green fluorescent protein were highly infectious but not cytopathic. Thus, env can accelerate cell death chiefly as an entry function, but one or more viral functions other than env or nef is essential for necrosis of CD4 ؉ T cells induced by HIV-1.
HIV induces modulation of functionally important cellular antigens
Clinical & Experimental Immunology, 2008
Infection of T lymphoblastoid CEM cells with the IIIB isolate of HIV-1 results in modulation of the expression of several cellular antigens in addition to the CD4 molecule. The intercellular adhesion receptor LFA-1 (CD1 la/CD18) and HLA-DR are markedly induced in the cytoplasm and at the cell surface, and the CD7 antigen is down-regulated, being virtually undetectable by sensitive immunocytochemical techniques in the infected cell population. These modulatory effects are to some degree dependent on the virus isolate examined, as the CBL-l British isolate did not induce comparable phenotypic changes in the CEM cell line. Furthermore, these effects are not reproduced by recombinant gpl20 (IIIB isolate) or p24 added exogenously to uninfected CEM cells. The CD7 molecule appears to play a regulatory role in T cell proliferation, and the LFA-I integrin molecule is involved in a wide range of immunologically important cell-cell interactions, as well as HIV-induced syncytium formation. The possible contributions of such effects to the pathogenesis of HIV infection are considered.
Interactions of HIV-1 with antigen-presenting cells
Immunology and Cell Biology, 1999
There is currently much interest in the numerical and functional loss of antigen-presenting cells (APC) in HIV-1 disease and the contribution that this may make to HIV-1 pathology. The HIV-1 virus can interfere with the normal function of APC in a number of ways involving inappropriate signalling. These include changes in cytokine balance, cell-surface molecule expression and intracellular signalling pathways. This review examines how HIV-1 is able to disregulate APC function and discusses possible outcomes for the function of the immune system.