Reaching the right destination is of vital importance for molecules, proteins, organelles, and cargoes. Thus, intracellular traffic is continuously controlled and regulated by several proteins taking part in the process. Viruses exploit this machinery, and viral proteins regulating intracellular transport have been identified as they represent valuable tools to understand and possibly direct molecules targeting and delivery. Deciphering the molecular features of viral proteins contributing to (or determining) this dynamic phenotype can eventually lead to a virus-independent approach to control cellular transport and delivery. From this virus-independent perspective we looked at U(S)9, a virion component of Herpes Simplex Virus involved in anterograde transport of the virus inside neurons of the infected host. As the natural cargo of U(S)9-related vesicles is the virus (or its parts), defining its autonomous, virus-independent role in vesicles transport represents a prerequisite to make U(S)9 a valuable molecular tool to study and possibly direct cellular transport. To assess the extent of this autonomous role in vesicles transport, we analyzed U(S)9 behavior in the absence of viral infection. Based on our studies, Us9 behavior appears similar in different cell types; however, as expected, the data we obtained in neurons best represent the virus-independent properties of U(S)9. In these primary cells, transfected U(S)9 mostly recapitulates the behavior of U(S)9 expressed from the viral genome. Additionally, ablation of two major phosphorylation sites (i.e. Y32Y33 and S34ES36) have no effect on protein incorporation on vesicles and on its localization on both proximal and distal regions of the cells. These results support the idea that, while U(S)9 post-translational modification may be important to regulate cargo loading and, consequently, virion export and delivery, no additional viral functions are required for U(S)9 role in intracellular transport.
Molecular Features Contributing to Virus-Independent Intracellular Localization and Dynamic Behavior of the Herpesvirus Transport Protein U(S)9
Creators
Manuela Pedrazzi - University of Bologna
Bradley Nash - Drexel University
Olimpia Meucci - Drexel University
Renato Brandimarti - Drexel University
Publication Details
PloS one, v 9(8)
Publisher
Public Library Science
Number of pages
13
Grant note
R21MH097623 / NATIONAL INSTITUTE OF MENTAL HEALTH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH)
P30CA056036 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
DA15014; DA 32444 / National Institutes of Health (NIH); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
R01DA015014 / NATIONAL INSTITUTE ON DRUG ABUSE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA); European Commission
Resource Type
Journal article
Language
English
Academic Unit
Biochemistry and Molecular Biology; Pharmacology and Physiology
Web of Science ID
WOS:000341302700034
Scopus ID
2-s2.0-84940255164
Other Identifier
991019168377804721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool: