AEGiS-12IAC: Natural host resistance to SIV-induced AIDS: complexity of viral load and tissue tropism in African green monkeys.

12th International AIDS Conference

Geneva, Switzerland - June 28-July 3, 1998

Natural host resistance to SIV-induced AIDS: complexity of viral load and tissue tropism in African green monkeys.

Int Conf AIDS 1998 Jun 28-Jul 3; 12:25 (abstract no. 11217)

Allan J, Broussard S, Leighton KL, Ahuja S, Staprans S, Feinberg M;;; SW Foundation for Biomedical Research, San Antonio, TX, USA.

OBJECTIVES: To compare host and viral specific parameters in SIVagm infected African green monkeys and rhesus macaques for clues in understanding differences in their susceptibility to SIV pathogenesis.

METHODS: Quantitative competitive RT-PCR was used to determine viral load in plasma and CSF of infected monkeys. In addition, we amplified and sequenced viral DNA from brain and lymph node of a naturally infected AGM. Tissue variants were also compared for chemokine receptor usage.

RESULTS: High viral loads were detected in three naturally infected African green monkeys (approximately 10(6) RNA) eq./ml). In contrast, only low levels of proviral DNA were found in the peripheral blood lymphocytes (< 1 DNA copies/10(5) cells). The numbers of SIVagm infected cells in both lymphoid and non-lymphoid tissues was also relatively low ranging from 67 to 670 DNA copies/10(5) cells in the lymph node with the highest levels detected in gastrointestinal tract respectively. Viral RNA (> 10(5) RNA eq./ml) was also detected in cerebrospinal fluids of 2 monkeys coinciding with the isolation of cell-free SIVagm from the CNS. Sequence analysis of amplified V2-V5 env gene fragments shows a large degree of amino acid diversity (14%) among viruses isolated from different tissues of a naturally infected monkey. Brain derived SIVagm (sab-4br) replicated in 293 cells transfected with CCR5, but not CCR2b. Finally, addition of sCD4 to SIVagm allowed infection of CCR5 cells lacking CD4 expression.

CONCLUSIONS: The disparity between high viral loads of circulating cell-free virus both in plasma and CSF coupled with only low numbers of infected cells in tissue compartments commonly associated with HIV-1 suggests fundamental differences in host-viral interactions leading to the apathogenic state in green monkeys.

Keywords: AEGIS, SIV, Cercopithecus aethiops, Viral Load, Simian Acquired Immunodeficiency Syndrome, Acquired Immunodeficiency Syndrome, Tropism, Immunity, Natural, CD4-Positive T-Lymphocytes, RNA, Viral, Macaca mulatta, DNA, Viral, Lymph Nodes, Lymphoid Tissue, Reverse Transcriptase Polymerase Chain Reaction, HIV-1, Animal, immunology, ICA12
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