Nuclear envelope budding in herpesvirus nuclear egress may be negatively regulated, since the pUL31/pUL34 nuclear egress complex heterodimer can induce membrane budding without capsids when expressed ectopically or on artificial membranes , but not in the infected cell. We have previously described a pUL34 mutant that contained alanine substitutions at R158 and R161 and that showed impaired growth, impaired pUL31/pUL34 interaction, and unregulated budding. Here, we determine the phenotypic contributions of the individual substitutions to these phenotypes. Neither substitution alone was able to reproduce the impaired growth or nuclear egress complex (NEC) interaction phenotypes. Either substitution, however, could fully reproduce the unregulated budding phenotype, suggesting that misregulated budding may not substantially impair virus replication. In addition, the R158A substitution caused relocalization of the NEC to intranuclear punctate structures and recruited lamin A/C to these structures, suggesting that this residue might be important for recruitment of kinases for dispersal of nuclear lamins. Herpesvirus nuclear egress is a complex, regulated process coordinated by two virus proteins that are conserved among the herpesviruses that form a heterodimeric nuclear egress complex (NEC). The NEC drives budding of capsids at the inner nuclear membrane and recruits other viral and host cell proteins for disruption of the nuclear lamina, membrane scission, and fusion. The structural basis of individual activities of the NEC, apart from membrane budding, are not clear, nor is the basis of the regulation of membrane budding. Here, we explore the properties of NEC mutants that have an unregulated budding phenotype, determine the significance of that regulation for virus replication, and also characterize a structural requirement for nuclear lamina disruption.
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http://dx.doi.org/10.1128/JVI.00873-21 | DOI Listing |
Poult Sci
December 2024
Institute of Veterinary Medicine and Immunology, Sichuan Agricultural University, Chengdu 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu 611130, PR China; International Joint Research Center for Animal Disease Prevention and Control of Sichuan Province, Chengdu 611130, PR China; Engineering Research Center of Southwest Animal Disease Prevention and Control Technology, Ministry of Education of the People's Republic of China, Chengdu 611130, PR China; Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China.
Duck plague (DP), which is caused by duck plague virus (DPV), is an infectious disease that severely harms the waterfowl breeding industry. The UL14 protein (pUL14) is a tegument protein encoded by the UL14 gene, which is located in the unique long (UL) region of the DPV genome. DPV pUL14 plays a crucial role in viral replication, likely by interacting with host and viral proteins that have yet to be identified.
View Article and Find Full Text PDFEmerg Microbes Infect
December 2025
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, People's Republic of China.
The nuclear-cytoplasmic trafficking of matrix proteins (M) is essential for henipavirus budding, with M protein ubiquitination playing a pivotal role in this dynamic process. Despite its importance, the intricacies of the M ubiquitination cascade have remained elusive. In this study, we elucidate a novel mechanism by which Nipah virus (NiV), a highly pathogenic henipavirus, utilizes a ubiquitination complex involving the E2 ubiquitin-conjugating enzyme RAD6A and the E3 ubiquitin ligase RAD18 to ubiquitinate the virus's M protein, thereby facilitating its nuclear-cytoplasmic trafficking.
View Article and Find Full Text PDFJ Virol
November 2024
State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
Autographa californica multiple nucleopolyhedrovirus (AcMNPV) () is highly conserved in baculoviruses. Previous studies have shown that is required for the production of infectious budded virions (BVs). However, the functional role of in virion morphogenesis remains unknown.
View Article and Find Full Text PDFbioRxiv
September 2024
Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, United States of America.
Viruses
September 2024
Institute for Virology and Forschungszentrum Immuntherapie, University Medical Center of the Johannes Gutenberg-University, 55131 Mainz, Germany.
(1) Background: Intrinsic defense mechanisms are pivotal host strategies to restrict viruses already at early stages of their infection. Here, we addressed the question of how the autophagy receptor sequestome 1 (/p62, hereafter referred to as p62) interferes with human cytomegalovirus (HCMV) infection. (2) Methods: CRISPR/Cas9-mediated genome editing, mass spectrometry and the expression of p62 phosphovariants from recombinant HCMVs were used to address the role of p62 during infection.
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