Blockade of HIV-1 infection of New World monkey cells occurs primarily at the stage of virus entry.
Blockade of HIV-1 infection of New World monkey cells occurs primarily at the stage of virus entry.
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DOI：
10.1084/jem.20020468
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发表时间：
2002-08-19
期刊：
影响因子：
--
通讯作者：
Sodroski J
中科院分区：
文献类型：
--
作者：
LaBonte JA;Babcock GJ;Patel T;Sodroski J
HIV-1自然会感染黑猩猩和人类，但不会感染旧大陆的猴子，因为病毒进入细胞后会发生复制阻滞。为了了解HIV-1感染的物种特异性限制，研究了HIV-1感染新大陆猴细胞的能力。来自普通狨猴和松鼠猴的原代细胞支持HIV-1复制的每个阶段，除了病毒进入。有效的HIV-1进入通常需要结合病毒包膜糖蛋白和宿主细胞受体、CD4和CCR5或CXCR4趋化因子受体。HIV-1无法检测到结合或利用松鼠猴的CD4进入，而且狨猴的CD4与人的CD4相比效率也非常低。一种狨猴CD4的变体，其残基48和59被改变为人类CD4中发现的氨基酸，有效地支持HIV-1进入。狨猴和松鼠猴的CXCR4分子都支持HIV-1感染，但这两种动物的CCR5蛋白都只有轻微的功能。这些结果表明，新世界猴的CD4和CCR5蛋白代表了这些灵长类动物对HIV-1复制的主要限制。HIV-1包膜糖蛋白对常见狨猴受体的定向适应可能允许开发新世界猴HIV-1感染模型。
HIV-1 naturally infects chimpanzees and humans, but does not infect Old World monkeys because of replication blocks that occur after virus entry into the cell. To understand the species-specific restrictions operating on HIV-1 infection, the ability of HIV-1 to infect the cells of New World monkeys was examined. Primary cells derived from common marmosets and squirrel monkeys support every phase of HIV-1 replication with the exception of virus entry. Efficient HIV-1 entry typically requires binding of the viral envelope glycoproteins and host cell receptors, CD4 and either CCR5 or CXCR4 chemokine receptors. HIV-1 did not detectably bind or utilize squirrel monkey CD4 for entry, and marmoset CD4 was also very inefficient compared with human CD4. A marmoset CD4 variant, in which residues 48 and 59 were altered to the amino acids found in human CD4, supported HIV-1 entry efficiently. The CXCR4 molecules of both marmosets and squirrel monkeys supported HIV-1 infection, but the CCR5 proteins of both species were only marginally functional. These results demonstrate that the CD4 and CCR5 proteins of New World monkeys represent the major restriction against HIV-1 replication in these primates. Directed adaptation of the HIV-1 envelope glycoproteins to common marmoset receptors might allow the development of New World monkey models of HIV-1 infection.
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影响因子：
56.9
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