Murine herpesvirus pathogenesis: a model for the analysis of molecular mechanisms of human gamma herpesvirus infections.
Murine herpes virus (MHV), a natural pathogen originally isolated from free-living rodents, constitutes the most amenable animal model for human gamma herpesviruses. Based on DNA sequence homology, this virus was classified as Murid Herpesvirus 4 to subfamily Gammaherpesvirinae. Pilot studies in our laboratory, using mice inoculated by the intranasal route, showed that MHV infects macrophages, B lymphocytes, lung alveolar as well as endothelial cells. From the lungs the virus spreads via the bloodstream to spleen and bone marrow and via the lymphatics to the mediastinal lymph nodes. Similarly to other gamma herpesviruses, MHV established life-long latency maintained in host B lymphocytes and macrophages. An IM-like syndrome (per analogy to EBV) may develop during acute MHV infection, in which the atypical T/CD8+ lymphocytes eliminate viral DNA carrying B cells expressing the M2 latency associated protein. During latency, the MHV LANA (a KSHV LANA homologue) maintains the latent viral genome, assuring its copying and partition to new carrier cells in the course of division of the maternal cell. The nonproductive latency is turned onto virus replication by means of Rta protein. The chronic lymphoproliferative syndrome of unclear pathogenesis, which occurs in a certain part of latent MHV carriers, is related to the expression of gamma herpesvirus common latency-associated genes such as v-cyclin and/or to that of a virus-specific (M11/bcl-2) gene. This review attempts to summarize our knowledge concerning the function of MHV genes (either gamma herpesvirus common or MHV specific) related to immune evasion, latency and lymphoproliferation when highlighting the unsolved problems and/or controversial opinions.
Rajćáni
J
J
Institute of Virology, Slovak Academy of Sciences, Dubravská 9, 84505 Bratislava, Slovak Republic. viruraj@savba.sk
Kúdelová
M
M
D000818:Animals; D001402:B-Lymphocytes / Q000821:virology; D002353:Carrier State; D002908:Chronic Disease; D016213:Cyclins / Q000235:genetics; D004195:Disease Models, Animal; D018142:Gammaherpesvirinae / Q000235:genetics / Q000502:physiology*; D019254:Genes, bcl-2; D016679:Genome, Viral; D006566:Herpesviridae Infections / Q000821:virology*; D017874:Immediate-Early Proteins / Q000502:physiology; D008232:Lymphoproliferative Disorders / Q000821:virology; D008264:Macrophages / Q000821:virology; D015534:Trans-Activators / Q000502:physiology; D014412:Tumor Virus Infections / Q000821:virology*; D014764:Viral Proteins / Q000235:genetics; D017735:Virus Latency
C068382:BRLF1 protein, Human herpesvirus 4; D016213:Cyclins; D017874:Immediate-Early Proteins; C118862:M3 protein, Murine gammaherpesvirus; D015534:Trans-Activators; D014764:Viral Proteins