Generation of a replication-competent chimeric simian-human immunodeficiency virus carrying env from subtype C clinical isolate through intracellular homologous recombination

► Intracellular homologous recombination was employed to generate a new SHIV strain. ► The generated SHIV 97ZA012 carried nearly the entire Env of subtype C isolate 97ZA012. ► SHIV 97ZA012 replicated to high titers in monkey PBMCs, as did SIV239. ► SHIV 97ZA012 was infectious to monkey alveolar macrophages. ► The virus caused high viremia and pulmonary CD4+ T-cell depletion during the acute phase.