Abstract:
HIV-2EHO is representative of a subgroup of HIV-2 which demonstrates enhanced cytopathogenicity, increased replicative rate, and extended host range in vitro as compared to the prototype HIV-2ROD. As previously reported, HIV-2EHO infects M. nemestrina and causes an AIDS-like disease in 50% of the infected animals. We have performed three serial in vivo passages since the original inoculation in 1989. Each passage consisted in the transfer of whole blood from one HIV-2 infected macaque into two recipients. With the first two serial passages, all recipients became persistently infected; 50% progressed to CD4+ cell depletion and disease. The time from transfusion to CD4+ depletion was 20 weeks for 1/2 animals in the first in vivo passage and 8 weeks for 1/2 animals in the second in vivo passage. The third in vivo passage (1/93) resulted in 2/2 animals becoming virus positive with virus loads of 1/100 cells positive for infectious virus in peripheral blood and lymph node mononuclear cells and 2/2 animals became CD4+ cell depleted in peripheral blood by week 4 and in lymph node by week 16 post-transfusion. Virus isolated from the HIV-2EHO infected and disease-progressive animals from the second and third in vivo transmissions has an altered cellular tropism as compared to the original virus inoculum with respect to host cell permissivity to infection and replication; in particular, macaque PBMC have a greatly increased permissivity to the in vivo derived isolates relative to the original inoculum. We have initiated challenge studies in M. nemestrina using cell-free virus stock derived from one of the diseased animals in the second in vivo passage.
Keywords: Acquired Immunodeficiency Syndrome/IMMUNOLOGY/*PHYSIOPATHOLOGY/ TRANSMISSION Animal Antigens, CD4/ANALYSIS Blood Transfusion HIV-2/*PHYSIOLOGY/*PATHOGENICITY Lymph Nodes/IMMUNOLOGY Lymphocyte Depletion Macaca nemestrina T-Lymphocyte Subsets/IMMUNOLOGY Time Factors Virulence Virus Replication ABSTRACT 940730
M9470873
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