Camerini D, Seed B
Department of Genetics, Harvard Medical School, Boston, Massachusetts.
Cell. 1990 Mar 9;60(5):747-54. doi: 10.1016/0092-8674(90)90089-w.
HIV infection of chimpanzees results in a chronic viremia unaccompanied by the ultimately fatal immunodeficiency that marks HIV infection in man. We show here that expression of HIV envelope proteins allows syncytium formation between cells expressing human but not chimpanzee or macaque CD4. We find that the CD4 sequences regulating cell fusion lie outside the recognized virus binding site; in the simplest exchange, chimpanzee CD4 bearing human residue 87 supports syncytium formation, while human CD4 bearing chimpanzee residue 87 does not. Neither the equilibrium nor the forward rate constants for HIV-CD4 association are affected by substitution at position 87. Infection of human cells expressing chimpanzee CD4 is insensitive to lysosomotropic agents, suggesting that viral penetration under these circumstances does not require endocytosis. The benign course of HIV infection in chimpanzees may reflect the failure of the host to support direct cell to cell transmission of the virus.
黑猩猩感染HIV会导致慢性病毒血症，但不会出现人类感染HIV时最终致命的免疫缺陷。我们在此表明，HIV包膜蛋白的表达会促使表达人类CD4而非黑猩猩或猕猴CD4的细胞之间形成多核巨细胞。我们发现，调节细胞融合的CD4序列位于公认的病毒结合位点之外；在最简单的交换中，携带人类87位残基的黑猩猩CD4支持多核巨细胞形成，而携带黑猩猩87位残基的人类CD4则不支持。HIV与CD4结合的平衡常数和正向速率常数均不受87位取代的影响。感染表达黑猩猩CD4的人类细胞对溶酶体促渗剂不敏感，这表明在这些情况下病毒穿透不需要内吞作用。黑猩猩感染HIV后的良性病程可能反映了宿主无法支持病毒直接在细胞间传播。
