Preferential replication of FIV in activated CD4+CD25+T cells independent of cellular proliferation

Preferential replication of FIV in activated CD4+CD25+T cells independent of cellular proliferation
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DOI:
10.1016/j.virol.2004.01.014
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发表时间:
2004-04-10
期刊:
影响因子:
3.7
通讯作者:
Tompkins, MB
Tompkins, MB
中科院分区:
医学3区
文献类型:
--
作者:
Joshi, A;Vahlenkamp, TW;Tompkins, MB

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试图确定HIV-1潜伏期的研究已经证明,该病毒在CD 4+细胞亚群中作为潜伏性和生产性感染持续存在。然而,关于在体外静止T细胞中建立稳定的HIV-1感染的报道是有争议的。在本研究中,我们研究了初始和活化的CD 4(+)细胞亚群(以CD 25的差异表达区分)对猫免疫缺陷病毒(FIV)感染的易感性,它们复制病毒的能力,以及可能作为病毒在感染动物中持续存在的储存库。虽然CD 4(+)CD 25(+)和CD 4(+)CD 25(-)细胞在体外和体内都对FIV感染敏感,但当与白细胞介素-2(IL-2)一起培养时,只有CD 4(+)CD 25(+)细胞产生感染性病毒体。潜伏感染的CD 4(+)CD 25(-)细胞在伴刀豆素A(ConA)刺激后产生感染性病毒体,其与上调的CD 25表面表达相关。与CD 4(+)CD 25(-)细胞相反,CD 4(+)CD 25(+)细胞对有丝分裂原刺激无反应,并且无论是否感染FIV,对凋亡都具有相对抗性。CD 4(+)CD 25(+)细胞在IL-2存在下有效复制FIV的能力,但仍然对凋亡信号无反应性和无反应性,这表明这些细胞可能提供了生产性FIV感染的储存库。相反,CD 4(+)CD 25(-)细胞似乎建立了潜伏的病毒库,能够在刺激后重新激活。(C)2004年爱思唯尔公司All rights reserved.
Studies attempting to identify reservoirs of HIV-1 latency have documented that the virus persists as both a latent and productive infection in subsets of CD4+ cells. Reports regarding establishment of a stable HIV-1 infection in quiescent T cells in vitro, however, are controversial. In the present study, we investigated the susceptibility of naive and activated CD4(+) cell subsets (distinguished by differential expression of CD25) to feline immunodeficiency virus (FIV) infection, their ability to replicate the virus, and potentially act as a reservoir for virus persistence in infected animals. While both CD4(+)CD25(+) and CD4(+)CD25(-) cells are susceptible to FIV infection in vitro and in vivo, only CD4(+)CD25(+) cells produce infectious virions when cultured with interleukin-2 (IL-2). Latently infected CD4(+)CD25(-) cells produce infectious virions following ConcanvalinA (ConA) stimulation, which correlates with upregulated surface expression of CD25. In contrast to CD4(+)CD25(-) cells, CD4(+)CD25(+) cells remain unresponsive to mitogen stimulation and are relatively resistant to apoptosis whether or not infected with FIV. The ability of CD4(+)CD25(+) cells to replicate FIV efficiently in the presence of IL-2 but remain anergic and unresponsive to apoptotic signaling suggests that these cells may provide a reservoir of productive FIV infection. On the contrary, CD4(+)CD25(-) cells seem to establish as latent viral reservoirs capable of being reactivated after stimulation. (C) 2004 Elsevier Inc. All rights reserved.