| dc.description.abstract | Simian immunodeficiency virus (SIV) infection in rhesus macaques is considered the best available model for Human Immunodeficiency Virus type-1 (HIV -1) studies, but SIV structural proteins are not exactly similar to HIV -1. Therefore, studies with SIV may not produce similar results as humans infected with HIV -1. To overcome this problem, a chimeric VIruS between SIV and HIV-1 i.e. simian human immunodeficiency virus (SHIV 89.6P) was constructed in which the envelope region of the SIVmac was replaced with that of a pathogenic HIV-l. This chimera proved to be infectious for PM-1 cells as well as for baboon peripheral blood mononuclear cells (PBMCs).
This study aimed at developing a model for paediatric AIDS usmg SHIV 89.6P infection of newborn baboons. To investigate the infectivity and pathogenicity of SHIV 89.6P, a pair of newborn baboon was inoculated intravenously with cell free SHIV 89.6P. Following virus recovery from the infants, 10 TCID 50 per million bone marrow
cells from one baboon in the pair, was transfused into a second naive newborn baboon at two weeks post inoculation. Virus was recovered after two weeks from the second baboon and 104 TCID so of bone marrow cells from the animal transfused into a third naive newborn baboon. Two weeks later virus was recovered from the third newborn baboon and 102 TCIDso of its bone marrow cells transfused to a fourth baboon. Two newborn baboons were used as uninfected controls. All the transfusions consisted of 1ml fresh bone marrow.
The infants were housed with their mothers and monitored for viremia, antibody responses and clinical signs of disease. Blood samples were collected from all animals at birth and at weekly intervals for the first month then monthly thereafter. Virus load
was determined by limiting co-culture method. Virus presence was assayed by peR.
Anti-SHIV IgG antibody responses were measured by anti-gp41 and anti-gpl60 IgG antibody ELISA using plates coated with SIVmac and HIV -1 peptides and confirmed by western blot. CD4+ and CD8+ T-lymphocyte subsets were measured by Fluorescent
Activated Cell Sorter (FACS).
All baboons developed persistent viremia at 2-3 .weeks post inoculation and onwards with constantly high cell associated virus titres ranging between 101 to 104 TCIDso per million cells over the observation period of 8•months. SHIV 89.6P like HIV -1 strain
89.6 was found to be macrophage tropic. Anti-SHIV IgG antibody responses were observed at 2 weeks post inoculation with anti-SHIV specific antibody titres being as high as 3000. All infants mounted gag specific IgG antibodies against SIVmac core proteins as demonstrated by western blot using SIV antigen. Proviral gag and env
sequences were detected by nested PCR using SIV and HIV primers at 2 weeks post inoculation. The baboons had a decline in CD4+ T-Iymphocytes and developed persistent lymphadenopathy.
This study has shown that inoculation of SHIV89.6P induces a persistent infection with high antibody titres, reversal of CD4+ICD8+ cell ratio and clinical alterations which suggests that SHIV 89.6P is pathogenic for baboons. This model may be used to evaluate anti-HIV vaccines and prophylactic agents directed against HIV -1 en | |
