Expression of Murine CD80 by Herpes Simplex Virus 1 in Place of Latency-Associated Transcript (LAT) Can Compensate for Latency Reactivation and Anti-apoptotic Functions of LAT
Expression of Murine CD80 by Herpes Simplex Virus 1 in Place of Latency-Associated Transcript (LAT) Can Compensate for Latency Reactivation and Anti-apoptotic Functions of LAT
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DOI：
10.1128/jvi.01798-19
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发表时间：
2020-03-01
影响因子：
5.4
通讯作者：
Ghiasi, Homayon
中科院分区：
文献类型：
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作者：
Jaggi, Ujjaldeep;Matundan, Harry H.;Ghiasi, Homayon
野生型（WT）单纯疱疹病毒1型（HSV-1）潜伏期再激活的高比率取决于潜伏相关转录本（LAT）的抗凋亡活性。用杆状病毒凋亡抑制蛋白（cpIAP）或细胞FLIP（FLICE样抑制蛋白）基因替代LAT，WT潜伏期再激活表型恢复为LAT阴性[LAT（-）]病毒的表型，而表达白细胞介素-4（IL-4）或干扰素γ（IFN-γ）的类似重组病毒则没有。然而，表达cpIAP的HSV-1重组病毒不能恢复所有LAT功能。最近，我们报道了一个类似的重组病毒表达CD 80的地方LAT有更高的潜伏期比LAT无效的病毒再激活。本研究旨在确定这种表达CD 80的重组病毒是否可以恢复WT病毒观察到的所有LAT功能。我们的研究结果表明，过度表达的CD 80完全拯救LAT功能的潜伏期再激活，细胞凋亡和免疫衰竭，这表明LAT和CD 80有多个重叠functions.IMPORTANCE复发HSV-1引起的眼部感染可导致角膜瘢痕和失明。HSV-1潜伏相关转录物（LAT）的主要功能是建立高水平的潜伏期和再激活，从而促进眼部疾病的发展。在这里，我们表明，宿主CD 80 T细胞共刺激分子的功能与LAT相似，可以恢复LAT建立潜伏期，再激活和免疫衰竭的能力，以及诱导caspase 3，caspase 8，caspase 9和Bcl 2的表达。我们的研究结果表明，与其他几个先前测试的基因相比，表达CD 80的病毒可以完全补偿所有已知和测试的LAT功能。
High rates of wild-type (WT) herpes simplex virus 1 (HSV-1) latency reactivation depend on the anti-apoptotic activities of latency-associated transcript (LAT). Replacing LAT with the baculovirus inhibitor of apoptosis protein (cpIAP) or cellular FLIP (FLICE-like inhibitory protein) gene restored the WT latency reactivation phenotype to that of a LAT-minus [LAT(-)] virus, while similar recombinant viruses expressing interleukin-4 (IL-4) or interferon gamma (IFN-gamma) did not. However, HSV-1 recombinant virus expressing cpIAP did not restore all LAT functions. Recently, we reported that a similar recombinant virus expressing CD80 in place of LAT had higher latency reactivation than a LAT-null virus. The present study was designed to determine if this CD80-expressing recombinant virus can restore all LAT functions as observed with WT virus. Our results suggest that overexpression of CD80 fully rescues LAT function in latency reactivation, apoptosis, and immune exhaustion, suggesting that LAT and CD80 have multiple overlapping functions.IMPORTANCE Recurring ocular infections caused by HSV-1 can cause corneal scarring and blindness. A major function of the HSV-1 latency-associated transcript (LAT) is to establish high levels of latency and reactivation, thus contributing to the development of eye disease. Here, we show that the host CD80 T cell costimulatory molecule functions similarly to LAT and can restore the ability of LAT to establish latency, reactivation, and immune exhaustion as well as induce the expression of caspase 3, caspase 8, caspase 9, and Bcl2. Our results suggest that, in contrast to several other previously tested genes, CD80-expressing virus can completely compensate for all known and tested LAT functions.