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Characterization of M116.1p, a Murine Cytomegalovirus Protein Required for Efficient Infection of Mononuclear Phagocytes (CROSBI ID 313367)

Prilog u časopisu | izvorni znanstveni rad | međunarodna recenzija

Ružić, Tina ; Juranić Lisnić, Vanda ; Mahmutefendić Lučin, Hana ; Lenac Roviš, Tihana ; Železnjak, Jelena ; Cokarić Brdovčak, Maja ; Vrbanović, Ana ; Oreb, Deni ; Kveštak, Daria ; Gotovac Jerčić, Kristina et al. Characterization of M116.1p, a Murine Cytomegalovirus Protein Required for Efficient Infection of Mononuclear Phagocytes // Journal of virology, 96 (2022), 2; e0087621, 26. doi: 10.1128/jvi.00876-21

Podaci o odgovornosti

Ružić, Tina ; Juranić Lisnić, Vanda ; Mahmutefendić Lučin, Hana ; Lenac Roviš, Tihana ; Železnjak, Jelena ; Cokarić Brdovčak, Maja ; Vrbanović, Ana ; Oreb, Deni ; Kveštak, Daria ; Gotovac Jerčić, Kristina ; Borovečki, Fran ; Lučin, Pero ; Adler, Barbara ; Jonjić, Stipan ; Lisnić, Berislav

engleski

Characterization of M116.1p, a Murine Cytomegalovirus Protein Required for Efficient Infection of Mononuclear Phagocytes

Broad tissue tropism of cytomegaloviruses (CMVs) is facilitated by different glycoprotein entry complexes, which are conserved between human CMV (HCMV) and murine CMV (MCMV). Among the wide array of cell types susceptible to the infection, mononuclear phagocytes (MNPs) play a unique role in the pathogenesis of the infection as they contribute both to the virus spread and immune control. CMVs have dedicated numerous genes for the efficient infection and evasion of macrophages and dendritic cells. In this study, we have characterized the properties and function of M116, a previously poorly described but highly transcribed MCMV gene region that encodes M116.1p, a novel protein necessary for the efficient infection of MNPs and viral spread in vivo. Our study further revealed that M116.1p shares similarities with its positional homologs in HCMV and RCMV, UL116 and R116, respectively, such as late kinetics of expression, N-glycosylation, localization to the virion assembly compartment, and interaction with gH- a member of the CMVs fusion complex. This study, therefore, expands our knowledge about virally encoded glycoproteins that play important roles in viral infectivity and tropism. IMPORTANCE Human cytomegalovirus (HCMV) is a species-specific herpesvirus that causes severe disease in immunocompromised individuals and immunologically immature neonates. Murine cytomegalovirus (MCMV) is biologically similar to HCMV, and it serves as a widely used model for studying the infection, pathogenesis, and immune responses to HCMV. In our previous work, we have identified the M116 ORF as one of the most extensively transcribed regions of the MCMV genome without an assigned function. This study shows that the M116 locus codes for a novel protein, M116.1p, which shares similarities with UL116 and R116 in HCMV and RCMV, respectively, and is required for the efficient infection of mononuclear phagocytes and virus spread in vivo. Furthermore, this study establishes the α-M116 monoclonal antibody and MCMV mutants lacking M116, generated in this work, as valuable tools for studying the role of macrophages and dendritic cells in limiting CMV infection following different MCMV administration routes.

cytomegalovirus ; intranasal infection ; macrophages ; mononuclear phagocyte ; mouse cytomegalovirus ; viral assembly compartment ; viral pathogenesis ; virus entry

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Podaci o izdanju

96 (2)

2022.

e0087621

26

objavljeno

0022-538X

1098-5514

10.1128/jvi.00876-21

Povezanost rada

Temeljne medicinske znanosti

Poveznice