Skip to main content

ORIGINAL RESEARCH article

Front. Cell. Infect. Microbiol.
Sec. Molecular Viral Pathogenesis
Volume 14 - 2024 | doi: 10.3389/fcimb.2024.1399761

SNX27:Retromer:ESCPE-1-mediated early endosomal tubulation impacts cytomegalovirus replication

Provisionally accepted
Hana Mahmutefendić Lučin Hana Mahmutefendić Lučin 1,2*Pero Lucin Pero Lucin 1,2*Igor Štimac Igor Štimac 1Marina Marcelić Marina Marcelić 1Barbara Radić Barbara Radić 1Ivona Viduka Ivona Viduka 1Gordana Blagojević Zagorac Gordana Blagojević Zagorac 1,2Silvija Lukanović Jurić Silvija Lukanović Jurić 1Carmen Rožmanić Carmen Rožmanić 1Martin Messerle Martin Messerle 3Ilija Brizić Ilija Brizić 1
  • 1 Faculty of Medicine, University of Rijeka, Rijeka, Croatia
  • 2 University North, Koprivnica, Koprivnica-Krizevci, Croatia
  • 3 Hannover Medical School, Hanover, Lower Saxony, Germany

The final, formatted version of the article will be published soon.

    Cytomegaloviruses (CMVs) extensively reorganize the membrane system of the cell and establish a new structure as large as the cell nucleus called the assembly compartment (AC). Our previous studies on murine CMV (MCMV)-infected fibroblasts indicated that the inner part of the AC contains rearranged early endosomes, recycling endosomes, endosomal recycling compartments and trans-Golgi membrane structures that are extensively tubulated, including the expansion and retention of tubular Rab10 elements. An essential process that initiates Rab10-associated tubulation is cargo sorting and retrieval mediated by SNX27, Retromer, and ESCPE-1 (endosomal SNX-BAR sorting complex for promoting exit 1) complexes. The aim of this study was to investigate the role of SNX27:Retromer:ESCPE1 complexes in the biogenesis of pre-AC in MCMV-infected cells and subsequently their role in secondary envelopment and release of infectious virions. Here we show that SNX27:Retromer:ESCPE1-mediated tubulation is essential for the establishment of a Rab10-decorated subset of membranes within the pre-AC, a function that requires an intact F3 subdomain of the SNX27 FERM domain. Suppression of SNX27-mediated functions resulted in an almost tenfold decrease in the release of infectious virions. However, these effects cannot be directly linked to the contribution of SNX27:Retromer:ESCPE-1-dependent tubulation to the secondary envelopment, as suppression of these components, including the F3-FERM domain, led to a decrease in MCMV protein expression and inhibited the progression of the replication cycle. Thus, this study demonstrates a novel and important function of membrane tubulation within the pre-AC associated with the control of viral protein expression.

    Keywords: Cytomegalovirus, assembly compartment, beta-herpesvirus secondary envelopment, sorting nexin 27, tubular endosomes, retromer, ESCPE-1

    Received: 12 Mar 2024; Accepted: 23 Aug 2024.

    Copyright: © 2024 Mahmutefendić Lučin, Lucin, Štimac, Marcelić, Radić, Viduka, Blagojević Zagorac, Lukanović Jurić, Rožmanić, Messerle and Brizić. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Hana Mahmutefendić Lučin, Faculty of Medicine, University of Rijeka, Rijeka, Croatia
    Pero Lucin, Faculty of Medicine, University of Rijeka, Rijeka, Croatia

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.