Replicative fitness of CCR5-using and CXCR4-using human immunodeficiency virus type 1 biological clones

Replicative fitness of CCR5-using and CXCR4-using human immunodeficiency virus type 1 biological clones
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DOI:
10.1016/j.virol.2005.11.045
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发表时间:
2006-03-30
期刊:
影响因子:
3.7
通讯作者:
Vanham, G
Vanham, G
中科院分区:
医学3区
文献类型:
--
作者:
Ariën, KK;Gali, Y;Vanham, G

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绝大多数新的HIV-1感染是由嗜CCR5病毒引起的,而大约一半的HIV-1感染者在疾病加速进展之前表现出一种共受体转换(CCR5 (R5)到CXCR4 (X4))。艾滋病患者X4生长的潜在生物学机制仍然知之甚少。虽然X4病毒在体内与增加的“毒力”有关,但X4和R5病毒的体外复制和细胞致病性研究导致了相互矛盾的结论。研究了从4例艾滋病患者中分离的具有不同共受体趋向性的HIV-1生物克隆的复制适宜性。平均而言,R5和X4克隆在有丝分裂原激活的T细胞中复制得同样好。相比之下,X4变异更有效地从树突状细胞转移到自体CD4(+) T细胞。这些观察结果表明,X4病毒、DC和T细胞之间的相互作用可能有助于X4病毒在艾滋病患者中的优先生长。(C) 2005爱思唯尔公司版权所有。
CCR5-tropic viruses cause the vast majority of new HIV-1 infections while about half of the individuals infected with HIV-1 manifest a co-receptor switch (CCR5 (R5) to CXCR4 (X4)) prior to accelerated disease progression. The underlying biological mechanisms of X4 Outgrowth in AIDS patients are still poorly understood. Although X4 viruses have been associated with increased "virulence" in vivo, in vitro replication and cytopathicity studies of X4 and R5 viruses have led to conflicting Conclusions. We Studied the replicative fitness of HIV-1 biological clones with different co-receptor tropism, isolated from four AIDS patients. On average, R5 and X4 clones replicated equally well in mitogen-activated T cells. In contrast, X4 variants were transferred more efficiently from dendritic cells to autologous CD4(+) T cells. These observations Suggest that interaction between X4 Viruses, DC and T cells might contribute to the preferential outgrowth of X4 viruses in AIDS patients. (C) 2005 Elsevier Inc. All rights reserved.