The increasing prevalence of HIV-1 subtype B' in China and Southeast Asia calls for efforts to develop a relevant animal model to study viral transmission and pathogenesis. Because there are significant differences between subtype B' HIV-1 and other chimeric simian/human immunodeficiency viru (SHIVs) in the env gene, a novel SHIV, designated SHIV(B'WHU), was generated by replacing counterparts of SHIV(SF33) with tat/rev/vpu/env genes derived from a primary, CCR5-tropic, subtype B' HIV-1 strain of a Chinese patient. SHIV(B'WHU) was able to replicate in rhesus peripheral blood mononuclear cells and used CCR5 as its major coreceptor. Moreover, after serial passages in Chinese macaques, the in vivo infectivity of SHIV(B'WHU) was enhanced, yet no significant sequence changes were found in viral envelopes, and the virus did not change its CCR5-tropism. CD4(+) T-cell loss, however, was found in the intraepithelial lymphocytes of small intestines of infected macaques. Our findings have implications in understanding the early pathogenesis of SHIV(B'WHU) in Chinese macaques.