PMID- 34440611 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240403 IS - 2075-1729 (Print) IS - 2075-1729 (Electronic) IS - 2075-1729 (Linking) VI - 11 IP - 8 DP - 2021 Aug 23 TI - Arf GTPases Are Required for the Establishment of the Pre-Assembly Compartment in the Early Phase of Cytomegalovirus Infection. LID - 10.3390/life11080867 [doi] LID - 867 AB - Shortly after entering the cells, cytomegaloviruses (CMVs) initiate massive reorganization of cellular endocytic and secretory pathways, which results in the forming of the cytoplasmic virion assembly compartment (AC). We have previously shown that the formation of AC in murine CMV- (MCMV) infected cells begins in the early phase of infection (at 4-6 hpi) with the pre-AC establishment. Pre-AC comprises membranes derived from the endosomal recycling compartment, early endosomes, and the trans-Golgi network, which is surrounded by fragmented Golgi cisterns. To explore the importance of Arf GTPases in the biogenesis of the pre-AC, we infected Balb 3T3 cells with MCMV and analyzed the expression and intracellular localization of Arf proteins in the early phases (up to 16 hpi) of infection and the development of pre-AC in cells with a knockdown of Arf protein expression by small interfering RNAs (siRNAs). Herein, we show that even in the early phase, MCMVs cause massive reorganization of the Arf system of the host cells and induce the over-recruitment of Arf proteins onto the membranes of pre-AC. Knockdown of Arf1, Arf3, Arf4, or Arf6 impaired the establishment of pre-AC. However, the knockdown of Arf1 and Arf6 also abolished the establishment of infection. Our study demonstrates that Arf GTPases are required for different steps of early cytomegalovirus infection, including the establishment of the pre-AC. FAU - Pavisic, Valentino AU - Pavisic V AUID- ORCID: 0000-0003-2291-0278 AD - Department of Physiology and Immunology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia. FAU - Mahmutefendic Lucin, Hana AU - Mahmutefendic Lucin H AUID- ORCID: 0000-0001-8462-4686 AD - Department of Physiology and Immunology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia. AD - Nursing Department, University North, University Center Varazdin, Jurja Krizanica 31b, 42000 Varazdin, Croatia. FAU - Blagojevic Zagorac, Gordana AU - Blagojevic Zagorac G AUID- ORCID: 0000-0003-1249-3802 AD - Department of Physiology and Immunology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia. AD - Nursing Department, University North, University Center Varazdin, Jurja Krizanica 31b, 42000 Varazdin, Croatia. FAU - Lucin, Pero AU - Lucin P AD - Department of Physiology and Immunology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia. AD - Nursing Department, University North, University Center Varazdin, Jurja Krizanica 31b, 42000 Varazdin, Croatia. LA - eng GR - IP-2020-02-1323/Hrvatska Zaklada za Znanost/ GR - IP-2019-4-3582/Hrvatska Zaklada za Znanost/ GR - uniri-biomed-18-229/University of Rijeka/ GR - uniri-biomed-18-88/University of Rijeka/ GR - uniri-biomed-18-180/University of Rijeka/ PT - Journal Article DEP - 20210823 PL - Switzerland TA - Life (Basel) JT - Life (Basel, Switzerland) JID - 101580444 PMC - PMC8399710 OTO - NOTNLM OT - Arf GTPases OT - Rab10 OT - cytomegaloviruses OT - m06 OT - pre-assembly compartment COIS- The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. EDAT- 2021/08/28 06:00 MHDA- 2021/08/28 06:01 PMCR- 2021/08/23 CRDT- 2021/08/27 01:07 PHST- 2021/07/27 00:00 [received] PHST- 2021/08/16 00:00 [revised] PHST- 2021/08/18 00:00 [accepted] PHST- 2021/08/27 01:07 [entrez] PHST- 2021/08/28 06:00 [pubmed] PHST- 2021/08/28 06:01 [medline] PHST- 2021/08/23 00:00 [pmc-release] AID - life11080867 [pii] AID - life-11-00867 [pii] AID - 10.3390/life11080867 [doi] PST - epublish SO - Life (Basel). 2021 Aug 23;11(8):867. doi: 10.3390/life11080867.