Immunodeficiency in the absence of high viral load in pig-tailed macaques infected with simian immunodeficiency virus SIVsun or SIVlhoest
Immunodeficiency in the absence of high viral load in pig-tailed macaques infected with simian immunodeficiency virus SIVsun or SIVlhoest
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DOI：
10.1128/jvi.79.22.14044-14056.2005
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发表时间：
2005-11-01
影响因子：
5.4
通讯作者：
Hirsch, VM
中科院分区：
文献类型：
--
作者：
Beer, BE;Brown, CR;Hirsch, VM
已知猿猴免疫缺陷病毒（SIV）可导致其天然非洲猴宿主的无症状感染。然而，一些SIV毒株在实验性感染亚洲猕猴后能够诱导艾滋病样症状和死亡。为了进一步研究来自非洲猴的天然SIV分离株的毒力，用最近发现的两种新型慢病毒SIVhoest和SIVsun中的任一种静脉内接种猪尾（PT）猕猴。这两种病毒在其自然宿主中明显无致病性，但在PT猕猴中引起免疫缺陷。感染的特征是外周血和淋巴结中CD 4（+）淋巴细胞的进行性丢失、全身淋巴细胞耗竭、消耗综合征和机会性感染，如鸟分枝杆菌或卡氏肺孢子虫感染。然而，与猕猴的SIVsm/mac感染不同，PT猕猴的SIVhoest和SIVsun感染在慢性疾病阶段不伴有高病毒载量。此外，在设定点（感染后12周）的病毒载量和存活率之间没有显着的相关性，可以发现。五个八SIVhoest感染和三个四SIVsun感染的猕猴死于艾滋病在感染的前5年。因此，SIVsun和SMhoest感染的动物的存活时间明显长于SIVagm或SIVsm感染的猕猴。所有PT猕猴保持强烈的SIV抗体反应，尽管进展到SIV诱导的艾滋病。在低病毒血症的免疫缺陷的发展表明，猕猴的SIVIhoest和SIVsun感染可能模拟人类免疫缺陷病毒感染的发病机制的独特方面。
Simian immunodeficiency virus (SIV) is known to result in an asymptomatic infection of its natural African monkey host. However, some SIV strains are capable of inducing AIDS-like symptoms and death upon experimental infection of Asian macaques. To further investigate the virulence of natural SIV isolates from African monkeys, pig-tailed (PT) macaques were inoculated intravenously with either of two recently discovered novel lentiviruses, SIVIhoest and SIVsun. Both viruses were apparently apathogenic in their natural hosts but caused immunodeficiency in PT macaques. Infection was characterized by a progressive loss of CD4(+) lymphocytes in the peripheral blood and lymph nodes, generalized lymphoid depletion, a wasting syndrome, and opportunistic infections, such as Mycobacterium avium or Pneumocystis carinii infections. However, unlike SIVsm/mac infection of macaques, SIVIhoest and SIVsun infections in PT macaques were not accompanied by high viral loads during the chronic disease stage. In addition, no significant correlation between the viral load at set point (12 weeks postinfection) and survival could be found. Five out of eight SIVIhoest-infected and three out of four SIVsun-infected macaques succumbed to AIDS during the first 5 years of infection. Thus, the survival of SIVsun- and SMhoest-infected animals was significantly longer than that of SIVagm- or SIVsm-infected macaques. All PT macaques maintained strong SIV antibody responses despite progression to SIV-induced AIDS. The development of immunodeficiency in the face of low viremia suggests that SIVIhoest and SIVsun infections of macaques may model unique aspects of the pathogenesis of human immunodeficiency virus infection in humans.