Harvard Medical School, New England Primate Research Center, Division of Comparative Pathology, Southborough, Massachusetts, United States of America.
Case Western Reserve University School of Medicine, Department of Molecular Biology and Microbiology, Cleveland, Ohio, United States of America.
PLoS One. 2014 Jan 21;9(1):e84463. doi: 10.1371/journal.pone.0084463. eCollection 2014.
Analysis of rhesus macaques infected with a vpx deletion mutant virus of simian immunodeficiency virus mac239 (SIVΔvpx) demonstrates that Vpx is essential for efficient monocyte/macrophage infection in vivo but is not necessary for development of AIDS. To compare myeloid-lineage cell infection in monkeys infected with SIVΔvpx compared to SIVmac239, we analyzed lymphoid and gastrointestinal tissues from SIVΔvpx-infected rhesus (n = 5), SIVmac239-infected rhesus with SIV encephalitis (7 SIV239E), those without encephalitis (4 SIV239noE), and other SIV mutant viruses with low viral loads (4 SIVΔnef, 2 SIVΔ3). SIV+ macrophages and the percentage of total SIV+ cells that were macrophages in spleen and lymph nodes were significantly lower in rhesus infected with SIVΔvpx (2.2%) compared to those infected with SIV239E (22.7%), SIV239noE (8.2%), and SIV mutant viruses (10.1%). In colon, SIVΔvpx monkeys had fewer SIV+ cells, no SIV+ macrophages, and lower percentage of SIV+ cells that were macrophages than the other 3 groups. Only 2 SIVΔvpx monkeys exhibited detectable virus in the colon. We demonstrate that Vpx is essential for efficient macrophage infection in vivo and that simian AIDS and death can occur in the absence of detectable macrophage infection.
对感染了 SIVΔvpx（一种 vpx 缺失突变的猴免疫缺陷病毒）的恒河猴进行分析，结果表明 Vpx 对于体内单核细胞/巨噬细胞的高效感染是必需的，但对于 AIDS 的发展并非必需。为了比较感染 SIVΔvpx 和 SIVmac239 的猴子中的髓系细胞感染，我们分析了感染 SIVΔvpx 的恒河猴（n=5）、感染 SIVmac239 并伴有 SIV 脑炎的恒河猴（7 只 SIV239E）、无脑炎的恒河猴（4 只 SIV239noE）以及其他病毒载量较低的 SIV 突变病毒（4 只 SIVΔnef、2 只 SIVΔ3）的淋巴组织和胃肠道组织。感染 SIVΔvpx 的恒河猴脾脏和淋巴结中 SIV+巨噬细胞以及 SIV+细胞中巨噬细胞的比例（2.2%）明显低于感染 SIV239E（22.7%）、SIV239noE（8.2%）和 SIV 突变病毒（10.1%）的恒河猴。在结肠中，感染 SIVΔvpx 的恒河猴 SIV+细胞数量较少，没有 SIV+巨噬细胞，且 SIV+细胞中巨噬细胞的比例也低于其他 3 组。只有 2 只 SIVΔvpx 感染的恒河猴结肠中可检测到病毒。我们证明，Vpx 对于体内巨噬细胞的高效感染是必需的，在没有可检测到的巨噬细胞感染的情况下，也可能发生猿猴 AIDS 和死亡。
