Background:  HIV clade C, the most prevalent subtype, accounts for over half of all HIV infections worldwide. To evaluate safety and efficacy of AIDS vaccines in nonhuman primate models, a pathogenic clade C SHIV strain that uses CCR5 as co-receptor would be highly desirable. We generated and characterized such a pathogenic clade C SHIV strain.

Methods:  After the chronically infected rhesus monkey RPn-8 developed AIDS (CD4+ T cells <200), its peripheral blood mononuclear cells (PBMC) were co-cultivated with naïve monkey PBMC. Genomic DNA was isolated and amplified by polymerase chain reaction (PCR) to generate molecular pro-viral clones. The infectivity of such clones was tested in TZM-bl cells that express luciferase under the control of the HIV, and long-term repeat and co-receptor usage were examined using U87.CD4 cells and ghost cells expressing different co-receptors. PBMC from six macaques were infected by viruses generated by one of the clones of SHIV-1157ipd3. The susceptibility of SHIV-1157ipd3 to commonly used human monoclonal antibodies was studied in human PBMC.

Results:  The parental SHIV strain, from which SHIV-1157ipd3 evolved, contained Env of a recently transmitted pediatric HIV isolate from a Zambian infant. The full-length molecular clone, SHIV-1157ipd3, was infectious in TZM-bl cells and only used CCR5 as a co-receptor. It was highly replication-competent in the PBMC of all six randomly selected naïve macaques. In vitro, SHIV-1157ipd3 was sensitive to several human neutralizing monoclonal antibodies raised against HIV clade B. The uncloned version of our SHIV strain, SHIV-1157ipd, caused memory T-cell depletion and thrombocytopenia in a juvenile macaque within 3 months of inoculation.

Conclusions:  These results indicate that SHIV-1157ipd is a pathogenic R5 clade C SHIV. Because co-receptor usage and the gradual pathogenicity of SHIV-1157ipd reflect the tropism of the most frequently transmitted form of HIV and the disease progression pattern in humans, SHIV-1157ipd and/or SHIV-1157ipd3 may represent ideal strains to evaluate AIDS vaccines.

Keywords: pathogenic; R5-tropic; SHIV