Abstract:
We have previously reported acute HIV-1 infection in eight Macaca nemestrina (pigtailed macaques), inoculated with cell-associated and/or cell-free virus. HIV-1 was recovered from the PBMC from all eight animals during two to eight weeks post-inoculation and rarely thereafter. PCR analysis revealed HIV-1-specific DNA from PBMC at times when virus cultures were negative. These animals developed and maintained strong antibody responses to HIV-1 gag and env proteins, but only low levels of neutralizing antibodies were detected. Subsequently, we inoculated approximately forty M. nemestrina with six additional isolates and are examining the utility of this model in other HIV-1 studies, including maternal-fetal transmission and central nervous system involvement. Further, we have begun passage experiments in an effort to recover an HIV-1 isolate with increased M. nemestrina pathogenicity. Our HIV-2 studies have involved thirty M. nemestrina, inoculated with five strains of HIV-2. We have recovered a macaque-virulent HIV-2 isolate following in vivo serial passage of the EHO strain. This isolate is 100% infectious with 50% mortality and is associated with AIDS-like signs, such as marked CD4+ lymphocyte depletion, anemia, opportunistic infections, encephalitis and syncytial cells in the brain. Taken together, these data demonstrate the potential utility of the M. nemestrina as a primate model for studying infection (HIV-1 and HIV-2) and pathogenicity (HIV-2) of the human immunodeficiency viruses.
Keywords: Acquired Immunodeficiency Syndrome/BLOOD/IMMUNOLOGY/*MICROBIOLOGY/ TRANSMISSION Animal DNA, Viral/BLOOD Female HIV-1/ISOLATION & PURIF/*PATHOGENICITY HIV-2/ISOLATION & PURIF/*PATHOGENICITY Lymphocytes/MICROBIOLOGY Macaca nemestrina Polymerase Chain Reaction Pregnancy Pregnancy Complications, Infectious Virulence ABSTRACT 940730
M9470876
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