This could be explained in part by the observations that this virus can downregulate major histocompatibility complex class I expression and also restrict inflammatory cell responses by producing a chemokine-binding protein (M3 gene product). In addition, MHV-68 infection of unexpected anatomic sites, which might give significant insights into viral pathogenesis, may not be identified simply because the infected tissue is not sampled (16, 45). Herpesviruses cause significant human disease. GammaHV68 infection of BALB beta2m-/- mice results in lymphoproliferation and lymphoma, providing a valuable tool for identifying viral and host genes involved in gammaherpesvirus-associated malignancies. Given the ability of γHV68 to establish latent infection and induce diseases in immunocompromised hosts, γHV68 is a useful model for investigating control of chronic gammaherpesvirus infection. Evidence for a similar pathogenic potential of PLHV-1 was reported by Huang et al.
Additionally, we also report infection of neuronal cells by KSHV in vitro similar to that by EBV. Virgin IV, J. Thus, the studies provide direct evidence that the proliferation of latently infected B cells is critical for the establishment of chronic gammaHV68 infection. To assess the feasibility of mutagenesis of the cloned MHV-68 genome, a mutant virus with a deletion of open reading frame 4 was generated. Reinsertion of ORF74 into the mutant virus restored the wild-type phenotype. The M3 protein was also capable of blocking the function of human CC and CXC chemokines, indicating the potential for therapeutic applications.
Furthermore, DNA extracted from archived brain and muscle tissues was also positive in 29% (4/14) and 50% (7/14) of cases examined. The TMER4 mutant virus replicated normally in lungs and spread with normal kinetics and distribution to lung-draining lymph nodes, but it was significantly attenuated for infection of circulating blood cells and for latency establishment at peripheral sites. NK cells restricted lytic SSM infection independently of IFN-I, and SSM-derived virions spread to the spleen only when IFN-I responses and NK cells were both lacking. These findings demonstrate that the E3 ligase activity of mLANA contributes to gammaherpesvirus-driven GC B cell proliferation. The human gammaherpesviruses Epstein-Barr virus and Kaposi’s sarcoma-associated herpesvirus, show only very limited infection of nonprimates, so murine gammaherpesvirus 68 (MHV-68), a close relative of Kaposi’s sarcoma-associated herpesvirus (9, 31), has proved useful in identifying how gammaherpesvirus genes contribute to host colonization. Like PLHV-1 and -2, PLHV-3 was frequently found in the blood and in lymphoid organs of domestic and feral pigs from different geographic locations.
Global gene expression analysis using an MHV-68 DNA array showed that PGE(2) increased production of multiple viral gene products, and NS-398 inhibited production of many of the same genes. Electron microscopy revealed the presence of capsids in the nucleus of immature DCs but not in mature DCs. However, the contribution of STAT3 to gammaherpesvirus pathogenesis remains to be completely understood. Major capsid protein sequences from the three subfamilies have some similarity, which is closer between KSHV and CMV than between either virus and HSV. By comparing the immune response to this virus with a revertant virus that can persist, we were able to dissect the changes in the antiviral CD8(+) T-cell response that are induced by virus persistence. These findings may explain why ORF75c mutant viruses unable to degrade PML had no demonstrable phenotype after infection.
Multiple risk factors are postulated to exacerbate malarial disease, one being co-infections with other pathogens. The presence of this novel gammaherpesvirus was confirmed by viral metagenomics, while no other viruses other than four novel anelloviruses were detected. However, the precise contribution that gammaherpesvirus miRNAs make to viral life cycle and pathogenesis in vivo is unknown. This report shows that (i) the carboxyl terminus of MyD116 interacts with protein phosphatase 1alpha in yeast, and both MyD116 and gamma(1)34.5 interact with protein phosphatase 1alpha in vitro; (ii) protein synthesis in infected cells is strongly inhibited by okadaic acid, a phosphatase 1 inhibitor; and (iii) the alpha subunit in purified eIF-2 phosphorylated in vitro is specifically dephosphorylated by S10 fractions of wild-type infected cells at a rate 3000 times that of mock-infected cells, whereas the eIF-2alpha-P phosphatase activity of gamma(1)34.5- virus infected cells is lower than that of mock-infected cells. We now show that host shutoff is also a prominent consequence of murine gammaherpesvirus 68 (MHV68) infection, which is widely used as a model system to study pathogenesis of these viruses in vivo.