Sialic acid-binding Ig-like lectin-7 interacts with HIV-1 gp120 and facilitates infection of CD4pos T cells and macrophages.
Sialic acid-binding Ig-like lectin-7 interacts with HIV-1 gp120 and facilitates infection of CD4pos T cells and macrophages.
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DOI：
10.1186/1742-4690-10-154
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发表时间：
2013-12-13
期刊：
影响因子：
3.3
通讯作者：
Mavilio D
中科院分区：
文献类型：
--
作者：
Varchetta S;Lusso P;Hudspeth K;Mikulak J;Mele D;Paolucci S;Cimbro R;Malnati M;Riva A;Maserati R;Mondelli MU;Mavilio D
唾液酸结合Ig样凝集素-7（Siglec-7）在HIV-1感染病毒血症患者的自然杀伤（NK）细胞上的表达强烈降低。为了研究这种现象背后的机制，我们假设Siglec-7在与HIV-1包膜（Env）糖蛋白120（gp 120）相互作用后可能有助于感染CD 4pos靶细胞。Siglec-7以唾液酸依赖性方式结合gp 120 Env的能力促进T细胞和单核细胞衍生的巨噬细胞（MDM）的感染。事实上，HIV-I与可溶性Siglec-7（sSiglec-7）的预孵育增加了不组成型表达Siglec-7的CD 4pos T细胞的感染率。相反，Siglec-7的选择性阻断显著降低Siglec-7 pos MDM中的HIV-1感染程度。最后，sSiglec-7量在具有高水平HIV-1病毒血症的AIDS患者的血清中增加，并且与CD 4pos T细胞计数负相关。我们的研究结果表明，Siglec-7结合HIV-1，并有助于增强CD 4pos T细胞和MDM对感染的易感性。这种现象在HIV-1发病机制和疾病进展中起作用，如在存在慢性病毒复制的AIDS患者中观察到的sSiglec-7的高血清水平与低CD 4pos T细胞计数之间的负相关性所表明的。
Sialic acid-binding Ig-like lectin-7 (Siglec-7) expression is strongly reduced on natural killer (NK) cells from HIV-1 infected viremic patients. To investigate the mechanism(s) underlying this phenomenon, we hypothesized that Siglec-7 could contribute to the infection of CD4pos target cells following its interaction with HIV-1 envelope (Env) glycoprotein 120 (gp120). The ability of Siglec-7 to bind gp120 Env in a sialic acid-dependent manner facilitates the infection of both T cells and monocyte-derived macrophages (MDMs). Indeed, pre-incubation of HIV-1 with soluble Siglec-7 (sSiglec-7) increases the infection rate of CD4pos T cells, which do not constitutively express Siglec-7. Conversely, selective blockade of Siglec-7 markedly reduces the degree of HIV-1 infection in Siglec-7pos MDMs. Finally, the sSiglec-7 amount is increased in the serum of AIDS patients with high levels of HIV-1 viremia and inversely correlates with CD4pos T cell counts. Our results show that Siglec-7 binds HIV-1 and contributes to enhance the susceptibility to infection of CD4pos T cells and MDMs. This phenomenon plays a role in HIV-1 pathogenesis and in disease progression, as suggested by the inverse correlation between high serum level of sSiglec-7 and the low CD4pos T cell count observed in AIDS patients in the presence of chronic viral replication.
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影响因子：
4.4
作者：
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影响因子：
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作者：
KAZAZI, F;MATHIJS, JM;CUNNINGHAM, AL
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