Gag-Gag Interactions Are Insufficient to Fully Stabilize and Order the Immature HIV Gag Lattice.
Gag-Gag Interactions Are Insufficient to Fully Stabilize and Order the Immature HIV Gag Lattice.
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DOI：
10.3390/v13101946
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发表时间：
2021-09-28
期刊：
影响因子：
--
通讯作者：
Saffarian S
中科院分区：
文献类型：
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作者：
Saha I;Preece B;Peterson A;Durden H;MacArthur B;Lowe J;Belnap D;Vershinin M;Saffarian S
未成熟的HIV病毒粒子在CA-NTD、CA-CTD和SP1区域中具有显著有序的Gag分子晶格。这种排序在HIV成熟过程中起着重要作用。为了测试Gag晶格在体内形成的条件，我们通过在哺乳动物细胞中仅表达HIV Gag来组装病毒样颗粒（VLP）。在这里，我们表明，这些VLP纳入了类似数量的Gag分子相比，未成熟的HIV病毒粒子。然而，在这些VLP中，Gag分子以10 nm 2/s的伪扩散速率扩散，这种伪扩散在蜂毒肽的存在下被废除，并且对SP1区域内的突变敏感。使用cryotomography，我们表明，不像不成熟的HIV病毒粒子，在加格的VLP的CA-CTD和SP1区域显着不那么有序。我们的观察结果表明，在未成熟的HIV病毒粒子，其他病毒因子除了Gag，有助于在CA-CTD和SP1区域的排序。
Immature HIV virions harbor a lattice of Gag molecules with significant ordering in CA-NTD, CA-CTD and SP1 regions. This ordering plays a major role during HIV maturation. To test the condition in which the Gag lattice forms in vivo, we assembled virus like particles (VLPs) by expressing only HIV Gag in mammalian cells. Here we show that these VLPs incorporate a similar number of Gag molecules compared to immature HIV virions. However, within these VLPs, Gag molecules diffuse with a pseudo-diffusion rate of 10 nm2/s, this pseudo-diffusion is abrogated in the presence of melittin and is sensitive to mutations within the SP1 region. Using cryotomography, we show that unlike immature HIV virions, in the Gag lattice of VLPs the CA-CTD and SP1 regions are significantly less ordered. Our observations suggest that within immature HIV virions, other viral factors in addition to Gag, contribute to ordering in the CA-CTD and SP1 regions.