title: Activation of Vav by the gammaherpesvirus M2 protein contributes to the establishment of viral latency in B lymphocytes.
abstract: Gammaherpesviruses subvert eukaryotic signaling pathways to favor latent infections in their cellular reservoirs. To this end, they express proteins that regulate or replace functionally specific signaling proteins of eukaryotic cells. Here we describe a new type of such viral-host interaction that is established through M2, a protein encoded by murine gammaherpesvirus 68. M2 associates with Vav proteins, a family of phosphorylation-dependent Rho/Rac exchange factors that play critical roles in lymphocyte signaling. M2 expression leads to Vav1 hyperphosphorylation and to the subsequent stimulation of its exchange activity towards Rac1, a process mediated by the formation of a trimolecular complex with Src kinases. This heteromolecular complex is coordinated by proline-rich and Src family-dependent phosphorylated regions of M2. Infection of Vav-deficient mice with gammaherpesvirus 68 results in increased long-term levels of latency in germinal center B lymphocytes, corroborating the importance of the M2/Vav cross talk in the process of viral latency. These results reveal a novel strategy used by the murine gammaherpesvirus family to subvert the lymphocyte signaling machinery to its own benefit.
authors.affiliation: Instituto Gulbenkian de Ciência, Oeias, Portugal.
authors.forename: Lénia
authors.initials: L
authors.lastname: Rodrigues
authors.forename: Marta
authors.initials: M
authors.lastname: Pires de Miranda
authors.forename: María J
authors.initials: MJ
authors.lastname: Caloca
authors.forename: Xosé R
authors.initials: XR
authors.lastname: Bustelo
authors.forename: J Pedro
authors.initials: JP
authors.lastname: Simas
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000821:virology*; D051379:Mice; D010766:Phosphorylation; D051567:Proto-Oncogene Proteins c-vav / Q000378:metabolism*; D020239:Receptor Cross-Talk; D018144:Rhadinovirus / Q000737:chemistry / Q000502:physiology*; D014763:Viral Matrix Proteins / Q000502:physiology*; D017735:Virus Latency; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D051567:Proto-Oncogene Proteins c-vav; D014763:Viral Matrix Proteins; D020830:rac1 GTP-Binding Protein