Host Derivation of Sindbis Virus Influences Mammalian Type I Interferon Response to Infection.
Host Derivation of Sindbis Virus Influences Mammalian Type I Interferon Response to Infection.
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DOI：
10.3390/v15081685
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发表时间：
2023-08-03
期刊：
影响因子：
--
通讯作者：
Hardy RW
中科院分区：
文献类型：
--
作者：
Crawford JM;Buechlein AM;Moline DA;Rusch DB;Hardy RW
虫媒病毒的定义是它们在蚊子媒介和哺乳动物宿主中复制的能力。有很好的证据表明，虫媒病毒为其后代感染下一宿主做好了准备，例如通过其外糖蛋白的差异糖基化或包装宿主核糖体亚基。我们和其他人之前已经证明，蚊子来源的病毒比哺乳动物来源的病毒更有效地感染哺乳动物细胞。这些观察结果与虫媒病毒获得宿主特异性适应一致，我们假设，来自哺乳动物宿主或蚊子媒介的病毒在感染哺乳动物宿主时引起不同的反应。在这里，我们对人类胚胎肾脏293(HEK-293)细胞对蚊子(白纹伊蚊，C7/10)或哺乳动物(Baby Hamster Kidney，BHK-21)衍生的辛德比斯病毒(SINV)感染的转录反应进行了RNA测序分析。我们表明，与感染BHK衍生病毒相比，C7/10衍生病毒感染导致HEK-293细胞中更强大的转录反应。令人惊讶的是，尽管感染效率更高，但我们发现C7/10来源的病毒感染时干扰素-β(干扰素-β)和干扰素刺激基因(Isg)的转录本比感染BHK来源的病毒增加。然而，在感染C7/10衍生病毒的HEK-293细胞中，干扰素刺激基因的翻译水平较低，与转录反应形成鲜明对比。这种对ISG翻译的抑制反映了在感染C7/10衍生病毒后宿主细胞翻译的更快的全面关闭。最后，我们发现C7/10衍生病毒感染HEK-293细胞导致磷酸化真核翻译延长因子-2(EEF2)水平升高，从而确定了导致宿主翻译更快关闭的潜在机制。我们推测，在感染蚊源病毒的哺乳动物细胞中，宿主翻译的快速关闭起到了对抗干扰素-β刺激的转录反应的作用。
Arboviruses are defined by their ability to replicate in both mosquito vectors and mammalian hosts. There is good evidence that arboviruses “prime” their progeny for infection of the next host, such as via differential glycosylation of their outer glycoproteins or packaging of host ribosomal subunits. We and others have previously shown that mosquito-derived viruses more efficiently infect mammalian cells than mammalian-derived viruses. These observations are consistent with arboviruses acquiring host-specific adaptations, and we hypothesized that a virus derived from either the mammalian host or mosquito vector elicits different responses when infecting the mammalian host. Here, we perform an RNA-sequencing analysis of the transcriptional response of Human Embryonic Kidney 293 (HEK-293) cells to infection with either mosquito (Aedes albopictus, C7/10)- or mammalian (Baby Hamster Kidney, BHK-21)-derived Sindbis virus (SINV). We show that the C7/10-derived virus infection leads to a more robust transcriptional response in HEK-293s compared to infection with the BHK-derived virus. Surprisingly, despite more efficient infection, we found an increase in interferon-β (IFN-β) and interferon-stimulated gene (ISG) transcripts in response to the C7/10-derived virus infection versus the BHK-derived virus infection. However, translation of interferon-stimulated genes was lower in HEK-293s infected with the C7/10-derived virus, starkly contrasting with the transcriptional response. This inhibition of ISG translation is reflective of a more rapid overall shut-off of host cell translation following infection with the C7/10-derived virus. Finally, we show that the C7/10-derived virus infection of HEK-293 cells leads to elevated levels of phosphorylated eukaryotic translation elongation factor-2 (eEF2), identifying a potential mechanism leading to the more rapid shut-off of host translation. We postulate that the rapid shut-off of host translation in mammalian cells infected with the mosquito-derived virus acts to counter the IFN-β-stimulated transcriptional response.
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影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
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影响因子：
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Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
通讯作者：
Hubbard TJ