Host-virus relationships in pathogenic and nonpathogenic SIV infections.
Int Conf AIDS 1996 Jul 7-12; 11:14 (abstract no. We.A.400) Grant RM, Kaur A, Johnson RP, McClure H, Staprans S, Feinberg MB; Office of AIDS Research, NIH, Bethesda, MD. Fax: 301-496-4843. E-mail: mark_feinberg@nih.gov.
To investigate the basis for asymptomatic SIV infection in naturally-infected sooty mangabeys (SMMs) quantitative-competitive PCR (QC-PCR) (to measure viral load) and heteroduplex mobility shift (HMA) assays were developed for SIVsmm and the SIVsmm-related virus SIVmac that induces AIDS in rhesus macaques. Interestingly, naturally infected, healthy SMMs display levels of active SIV replication that equal, and in some cases exceed, those seen in macaques with advanced SIV-induced immunodeficiency. Further, the population of virus present in infected SMMs displays extensive nucleotide sequence variation. SIV-infected SMMs have no demonstrable CTL activity against SIV antigen- expressing cells, but do mount a humoral immune response to viral antigens. The nature and pattern of nucleotide sequence variation seen in infected SMMs is consistent with diversification resulting from genetic drift rather than immune selection. These data suggest that naturally-infected SMMs are immunologically tolerant to SIV at the CD8 T cell level, and that the immune responses of SMMs do not modify the level of virus replication to any significant extent. That SIV replication proceeds at high levels without CD4 depletion and the finding of histologically normal lymphoid tissues in infected animals indicates that the interaction of virus with SMM host cells is not cytopathic. Results from tissue culture studies support this conclusion, and ongoing studies are focused on elucidating the basis for this lack of cytopathicity. The evolution of SIVsmm in its natural host may have selected for a non-cytopathic course of virus infection of host cells, and the limited antiviral immune response seen may be an important adaptation acting to prevent immunopathologic consequences of the infection. In species that are not natural hosts for T cell-tropic lentiviruses, and where the virus infection has direct cytopathic consequences (including rhesus macaques and humans), an effective host immune response may, in contrast, be necessary to control virus replication and mitigate the rate of disease progression.
Keywords: AEGIS, SIV, Cercocebus atys, Macaca mulatta, Macaca, Virus Replication, CD8-Positive T-Lymphocytes, CD4-Positive T-Lymphocytes, Antigens, Viral, T-Lymphocytes, Cytotoxic, Viral Load, T-Lymphocyte Subsets, T-Lymphocytes, Animal, Human, virology, ICA11
