title: A gammaherpesvirus uses alternative splicing to regulate its tropism and its sensitivity to neutralization.
abstract: Human gammaherpesviruses are associated with the development of lymphomas and epithelial malignancies. The heterogeneity of these tumors reflects the ability of these viruses to route infection to different cell types at various stages of their lifecycle. While the Epstein Barr virus uses gp42--human leukocyte antigen class II interaction as a switch of cell tropism, the molecular mechanism that orientates tropism of rhadinoviruses is still poorly defined. Here, we used bovine herpesvirus 4 (BoHV-4) to further elucidate how rhadinoviruses regulate their infectivity. In the absence of any gp42 homolog, BoHV-4 exploits the alternative splicing of its Bo10 gene to produce distinct viral populations that behave differently based on the originating cell. While epithelial cells produce virions with high levels of the accessory envelope protein gp180, encoded by a Bo10 spliced product, myeloid cells express reduced levels of gp180. As a consequence, virions grown in epithelial cells are hardly infectious for CD14+ circulating cells, but are relatively resistant to antibody neutralization due to the shielding property of gp180 for vulnerable entry epitopes. In contrast, myeloid virions readily infect CD14+ circulating cells but are easily neutralized. This molecular switch could therefore allow BoHV-4 to promote either, on the one hand, its dissemination into the organism, or, on the other hand, its transmission between hosts.
authors.affiliation: Immunology-Vaccinology Laboratory, Department of Infectious and Parasitic Diseases, Faculty of Veterinary Medicine, University of Liège, Liège, Belgium.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Machiels
authors.forename: Philip G
authors.initials: PG
authors.lastname: Stevenson
authors.forename: Alain
authors.initials: A
authors.lastname: Vanderplasschen
authors.forename: Laurent
authors.initials: L
authors.lastname: Gillet
mesh_terms: D017398:Alternative Splicing / Q000235:genetics / Q000276:immunology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D002417:Cattle; D002460:Cell Line; D026021:Herpesvirus 4, Bovine / Q000235:genetics / Q000276:immunology*; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000276:immunology; D011817:Rabbits; D014764:Viral Proteins / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D018950:Lipopolysaccharide Receptors; D014764:Viral Proteins