Effect of the US3 protein of bovine herpesvirus 5 on the actin cytoskeleton and apoptosis

• Published in: Veterinary microbiology Vol. 153; no. 3; pp. 361 - 366
• Main Authors: Ladelfa, María Fátima, Kotsias, Fiorella, Del Médico Zajac, María Paula, Van den Broeke, Céline, Favoreel, Herman, Romera, Sonia Alejandra, Calamante, Gabriela
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 15-12-2011; Elsevier
• Subjects: Actin cytoskeleton; Actins - metabolism; Alphaherpesvirinae; Animals; Apoptosis; Apoptosis - physiology; Biological and medical sciences; Bovine herpesvirus 5; Cattle; Cell Nucleus - enzymology; Cercopithecus aethiops; Cytoplasm - enzymology; Cytoskeleton - metabolism; Fundamental and applied biological sciences. Psychology; Herpesvirus 5, Bovine - enzymology; Microbiology; Microtubules - metabolism; Miscellaneous; Molecular Sequence Data; Mutation; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; US3 kinase-dead; Vero Cells; Viral Proteins - genetics; Viral Proteins - metabolism; Virology; US3 kinase-dead; Actin cytoskeleton; Bovine herpesvirus 5; Apoptosis; Enzyme; Herpesviridae; Transferases; Protein; Virus; Actin; Kinase; Bovine herpesvirus; Cytoskeleton; Veterinary
• ISSN: 0378-1135; 1873-2542
• DOI: 10.1016/j.vetmic.2011.05.037

The US3 protein is a unique protein kinase only present in the
Alphaherpesvirinae subfamily of the herpesviruses. Studies performed with several alphaherpesviruses demonstrated that the US3 protein is involved in cytoskeleton modifications during viral infection and displays anti-apoptotic activity. However, the US3 protein of BoHV-5 has not been studied up to now. As reported for other alphaherpesviruses, our results showed that BoHV-5 US3 confers resistance against apoptosis and induces cytoskeletal reorganization leading to cell rounding, actin stress fiber breakdown and cell projections that interconnect cells. The expression of a kinase-dead version of BoHV-5 US3 showed that the anti-apoptotic activity and the induction of cell projections are kinase-dependent whereas kinase activity is not absolutely required for actin stress fiber breakdown. Besides, the kinase-dead version of US3, but not the wild type protein, was found excluded from the nucleus. These results constitute the first report on the BoHV-5 US3 functions, and highlight that there are functional differences and similarities among US3 proteins of different alphaherpesviruses.