Luciw P A, Pratt-Lowe E, Shaw K E, Levy J A, Cheng-Mayer C
Department of Medical Pathology, University of California, Davis 95616, USA.
Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7490-4. doi: 10.1073/pnas.92.16.7490.
To elucidate the functions of human immunodeficiency virus type 1 (HIV-1) genes in a nonhuman primate model, we have constructed infectious recombinant viruses (chimeras) between the pathogenic molecular clone of simian immunodeficiency virus (SIV) SIVmac239 and molecular clones of HIV-1 that differ in phenotypic properties controlled by the env gene. HIV-1SF33 is a T-cell-line-tropic virus which induces syncytia, and HIV-1SF162 is a macrophage-tropic virus that does not induce syncytia. A DNA fragment encoding tat, rev, and env (gp160) of SIVmac239 has been replaced with the counterpart genetic region of HIV-1SF33 and HIV-1SF162 to derive chimeric recombinant simian/human immunodeficiency virus (SHIV) strains SHIVSF33 and SHIVSF162, respectively. In the acute infection stage, macaques inoculated with SHIVSF33 had levels of viremia similar to macaques infected with SIVmac239, whereas virus loads were 1/10th to 1/100th those in macaques infected with SHIVSF162. Of note is the relatively small amount of virus detected in lymph nodes of SHIVSF162-infected macaques. In the chronic infection stage, macaques infected with SHIVSF33 also showed higher virus loads than macaques infected with SHIVSF162. Virus persists for over 1 year, as demonstrated by PCR for amplification of viral DNA in all animals and by virus isolation in some animals. Antiviral antibodies, including antibodies to the HIV-1 env glycoprotein (gp160), were detected; titers of antiviral antibodies were higher in macaques infected with SHIVSF33 than in macaques infected with SHIVSF162. Although virus has persisted for over 1 year after inoculation, these animals have remained healthy with no signs of immunodeficiency. These findings demonstrate the utility of the SHIV/macaque model for analyzing HIV-1 env gene functions and for evaluating vaccines based on HIV-1 env antigens.
为阐明1型人类免疫缺陷病毒（HIV-1）基因在非人类灵长类动物模型中的功能，我们构建了猿猴免疫缺陷病毒（SIV）SIVmac239的致病分子克隆与HIV-1分子克隆之间的感染性重组病毒（嵌合体），这些HIV-1分子克隆在由env基因控制的表型特性上存在差异。HIV-1SF33是一种能诱导多核巨细胞形成的嗜T细胞系病毒，而HIV-1SF162是一种不诱导多核巨细胞形成的嗜巨噬细胞病毒。编码SIVmac239的tat、rev和env（gp160）的DNA片段已分别被HIV-1SF33和HIV-1SF162的对应基因区域取代，从而分别获得嵌合重组猿猴/人类免疫缺陷病毒（SHIV）毒株SHIVSF33和SHIVSF162。在急性感染阶段，接种SHIVSF33的猕猴的病毒血症水平与感染SIVmac239的猕猴相似，而病毒载量仅为感染SHIVSF162的猕猴的1/10至1/100。值得注意的是，在感染SHIVSF162的猕猴的淋巴结中检测到的病毒量相对较少。在慢性感染阶段，感染SHIVSF33的猕猴的病毒载量也高于感染SHIVSF162的猕猴。通过对所有动物的病毒DNA进行PCR扩增以及对部分动物进行病毒分离证明，病毒持续存在超过1年。检测到了抗病毒抗体，包括针对HIV-1 env糖蛋白（gp160）的抗体；感染SHIVSF33的猕猴的抗病毒抗体滴度高于感染SHIVSF162的猕猴。尽管接种后病毒已持续存在超过1年，但这些动物仍保持健康，没有免疫缺陷的迹象。这些发现证明了SHIV/猕猴模型在分析HIV-1 env基因功能以及评估基于HIV-1 env抗原的疫苗方面的实用性。
