1. Suppression of annexin A1 and its receptor reduces herpes simplex virus 1 lethality in mice.
- Author
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Wang, Li-Chiu, Wu, Shang-Rung, Yao, Hui-Wen, Ling, Pin, Perng, Guey-Chuen, Chiu, Yen-Chi, Hsu, Sheng-Min, and Chen, Shun-Hua
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PEPTIDE receptors ,ANNEXINS ,MICE ,GLYCOPROTEINS ,CARRIER proteins ,PROTEIN binding - Abstract
Herpes simplex virus 1 (HSV-1)-induced encephalitis is the most common cause of sporadic, fatal encephalitis in humans. HSV-1 has at least 10 different envelope glycoproteins, which can promote virus infection. The ligands for most of the envelope glycoproteins and the significance of these ligands in virus-induced encephalitis remain elusive. Here, we show that glycoprotein E (gE) binds to the cellular protein, annexin A1 (Anx-A1) to enhance infection. Anx-A1 can be detected on the surface of cells permissive for HSV-1 before infection and on virions. Suppression of Anx-A1 or its receptor, formyl peptide receptor 2 (FPR2), on the cell surface and gE or Anx-A1 on HSV-1 envelopes reduced virus binding to cells. Importantly, Anx-A1 knockout, Anx-A1 knockdown, or treatments with the FPR2 antagonist reduced the mortality and tissue viral loads of infected mice. Our results show that Anx-A1 is a novel enhancing factor of HSV-1 infection. Anx-A1-deficient mice displayed no evident physiology and behavior changes. Hence, targeting Anx-A1 and FPR2 could be a promising prophylaxis or adjuvant therapy to decrease HSV-1 lethality. Author summary: Herpes simplex virus 1 (HSV-1)-induced encephalitis is the most devastating consequence of HSV-1 infection, even in patients treated with anti-HSV-1 drugs. Moreover, encephalitis induced by drug-resistant HSV-1 has been reported in immunocompromised patients. Identifying the cellular factors in promoting HSV-1 replication, especially those increasing virus attachment and entry, could facilitate the development of alternative or adjuvant therapy. Here, we identified annexin A1 (Anx-A1) and its receptor, formyl peptide receptor 2 (FPR2), facilitating HSV-1 attachment to the cell surface. Suppression of Anx-A1 or blockage of FPR2 impaired HSV-1 attachment to cells, viral yields in cells, and HSV-1 lethality in mice. Moreover, blocking FPR2 decreased the replication of drug-resistant HSV-1 in BABL/c nude mice. Hence, targeting Anx-A1 and FPR2 could be alternative or adjuvant therapy for HSV-1 infection. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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