Stephens E B, Galbreath D, Liu Z Q, Sahni M, Li Z, Lamb-Wharton R, Foresman L, Joag S V, Narayan O
Department of Microbiology, Molecular Genetics and Immunology, Marion Merrell Dow Laboratory of Viral Pathogenesis, University of Kansas Medical Center, Kansas City 66160-7317, USA.
J Leukoc Biol. 1997 Jul;62(1):12-9. doi: 10.1002/jlb.62.1.12.
Microglia, alveolar macrophages, and Langerhans cells are representatives of cells of macrophage lineage that are susceptible to infection with HIV-1 and they play important roles in the pathogenesis of AIDS dementia, lymphoid interstitial pneumonia, and systemic viral invasion from mucosal surfaces, respectively. In contrast, elimination of CD4+ T cells with resultant development of immunosuppression and AIDS is thought to be reflective of the exclusive tropism of the virus for CD4+ T cells. Examination of these concepts in macaques infected with molecularly cloned strains of SIVmac suggested that all strains of the virus are both macrophage- and lymphocyte-tropic and that all aspects of pathogenesis including loss of CD4+ T cells are dependent on infection in both cell types. However, viral clones that caused productive lytic infection in macrophages were less virulent than those which caused persistent nonproductive infection. The former caused subclinical and even immunizing infections, whereas the latter caused activation and productive infection in CD4+ T cells, AIDS, and systemic infection, even after inoculation of the virus on mucosal surfaces. If these findings on SIVmac are relevant to HIV-1 disease, then demonstration that HIV-1 isolates are macrophage-tropic probably does not necessarily correlate with their pathogenic potential.
小胶质细胞、肺泡巨噬细胞和朗格汉斯细胞是巨噬细胞谱系细胞的代表，它们易受HIV-1感染，分别在艾滋病痴呆症、淋巴样间质性肺炎以及黏膜表面的全身性病毒侵袭的发病机制中发挥重要作用。相比之下，CD4+ T细胞的消除以及由此导致的免疫抑制和艾滋病的发展被认为反映了该病毒对CD4+ T细胞的独特嗜性。对感染了分子克隆的SIVmac毒株的猕猴进行的这些概念研究表明，该病毒的所有毒株都具有巨噬细胞嗜性和淋巴细胞嗜性，并且包括CD4+ T细胞丧失在内的发病机制的所有方面都依赖于两种细胞类型的感染。然而，在巨噬细胞中引起有效裂解感染的病毒克隆的毒性低于那些引起持续性非有效感染的病毒克隆。前者引起亚临床甚至免疫性感染，而后者即使在病毒接种于黏膜表面后，也会在CD4+ T细胞中引起激活和有效感染、导致艾滋病以及全身性感染。如果关于SIVmac的这些发现与HIV-1疾病相关，那么HIV-1分离株具有巨噬细胞嗜性的证明可能不一定与其致病潜力相关。
