Myxococcus xanthus social (S) gliding motility has been previously reported by us to require the chemotaxis homologues encoded by the dif genes. In addition, two cell surface structures, type IV pili and extracellular matrix fibrils, are also critical to M. xanthus S motility. We have demonstrated here that M. xanthus dif genes are required for the biogenesis of fibrils but not for that of type IV pili. Furthermore, the developmental defects of dif mutants can be partially rescued by the addition of isolated fibril materials. Along with the chemotaxis genes of various swarming bacteria and the pilGHIJ genes of the twitching bacterium Pseudomonas aeruginosa, the M. xanthus dif genes belong to a unique class of bacterial chemotaxis genes or homologues implicated in the biogenesis of structures required for bacterial surface locomotion. Genetic studies indicate that the dif genes are linked to the M. xanthus dsp region, a locus known to be crucial for M. xanthus fibril biogenesis and S gliding.

Murine gammaherpesvirus 68 (MHV-68 [also referred to as ␥HV68]) is phylogenetically related to Kaposi's sarcoma-associated herpesvirus (KSHV [also referred to as HHV-8]) and Epstein-Barr virus (EBV).Gammaherpesviruses are known to establish latency in lymphocytes and are associated with tumorigenesis (5-7, 10, 48). Two important human pathogens in the gammaherpesvirus subfamily of herpesviruses are Kaposi's sarcoma-associated herpesvirus (KSHV [also referred to as HHV-8]) and EpsteinBarr virus (EBV). KSHV and EBV are associated with several malignancies, including B-cell lymphomas, nasopharyngeal carcinoma, and Kaposi's sarcoma (22,23,27,30,32). Studies of KSHV and EBV are limited by the lack of cell lines able to support efficient productive infection and by the restricted host ranges of the viruses (11, 33). Murine gammaherpesvirus 68 (MHV-68 [also referred to as ␥HV68]) is another member of the gammaherpesvirus subfamily. However, in vitro cell culture systems are available to study productive de novo infection by MHV-68, as well as latency and reactivation (34, 40). MHV-68 forms plaques on monolayers of many cell lines, making it possible to genetically manipulate the viral genome. MHV-68 establishes lytic and latent infections in laboratory mice (47), providing a system for examining host-virus interactions (24,25,36,42,43). These characteristics of MHV-68 make it possible to examine the functions of individual viral genes at various points during the viral life cycle, including de novo infection. De novo infection analyses have not been possible for other gammaherpesviruses such as EBV and KSHV.Herpesviruses have two distinct life cycle phases, latency and lytic replication. Reactivation from latency to lytic replication is essential for transmission of the virus from host to host and thus is one important aspect of herpesvirus biology. A viral protein, replication and transcription activator (RTA) is primarily encoded by open reading frame (ORF) 50, which is well conserved among gammaherpesviruses. RTA is necessary and sufficient to reactivate MHV-68 and drive the lytic cycle to completion in latently infected B cells (14,19,54,55). Similarly, KSHV RTA has been shown to be sufficient to reactivate the virus from latently infected B cells derived from KSHVassociated lymphomas (20,46). Although two EBV proteins, RTA and ZEBRA, function in a cooperative manner to reactivate the viral lytic cycle (3, 18, 21), RTA alone can disrupt latency in some latently infected cell lines (31, 56). These studies indicate that RTA of gammaherpesviruses plays a conserved role in virus reactivation.We have constructed custom membrane arrays representing nearly all of the known and predicted MHV-68 ORFs to explore the patterns of viral gene expression. To illustrate the value of genome-wide transcription analysis, we used the MHV-68 DNA arrays to identify a novel regulatory element for a specific gene, to identify latency-associated transcripts not previously recognized, and to define the genome-wide effects of a specific gene...

Summary A conserved herpesviral kinase has been shown to play multiple vital roles in the life cycle of herpesviruses. ORF36, the kinase of murine gamma-herpesvirus 68 (MHV-68), was identified to counteract antiviral type I interferon (IFN) response through the screening of mutant viruses. ORF36 binds to activated interferon regulatory factor 3 (IRF-3) in the nucleus and inhibits the interaction between the IRF-3 and the co-transcriptional activator CBP, thereby suppressing the recruitment of RNA polymerase II to interferon beta promoter. Although the conserved kinase activity is not absolutely required for this interaction, the anti-IFN function of ORF36 is conserved among all herpesvirus subfamilies. Mutant viruses without ORF36 induce more interferon response and are attenuated both in vitro and in vivo. Our data suggest that herpesviruses have evolved an inhibitor of antiviral IFN defense within their conserved kinase, which is critical for herpesvirus to evade host immune control and persist in a host.

Gammaherpesviruses establish life-long persistency inside the host and cause various diseases during their persistent infection. However, the systemic interaction between the virus and host in vivo has not been studied in individual hosts continuously, although such information can be crucial to control the persistent infection of the gammaherpesviruses.

Gammaherpesviruses are known to establish latency in lymphocytes and are associated with tumorigenesis. Two important human pathogens in the family are Kaposi's sarcomaassociated herpesvirus (KSHV; also referred to as HHV-8) and Epstein-Barr virus (EBV). KSHV and EBV are associated with several malignancies, including B-cell lymphomas, nasopharyngeal carcinoma, and Kaposi's sarcoma. Studies of KSHV and EBV are limited by the lack of cell lines to support efficient productive infection and by their restricted host ranges. Murine gammaherpesvirus 68 (MHV-68; also referred to as ␥HV68) is also a member of the gammaherpesvirus family. Unlike KSHV or EBV, in vitro cell culture systems are available to study productive de novo infection by MHV-68, as well as latency and reactivation. MHV-68 forms plaques on monolayers of many cell lines, making it relatively straightforward to genetically manipulate the viral genome. MHV-68 can also establish productive and latent infections in laboratory mice (23), which allows us to pursue questions that relate to host-virus interactions (16,17,20,21). Because of these advantages, MHV-68 offers an excellent model to study the biology and pathogenesis of gammaherpesviruses.Herpesviruses have two distinct phases of their life cycle, productive infection and latency. Reactivation from latency to productive infection is essential for transmission of the virus from host to host and thus is one important aspect of herpesvirus biology. The molecular mechanisms of reactivation have been extensively studied in KSHV and EBV. Cell lines derived from KSHV-or EBV-associated lymphomas are latently infected with virus. A viral protein, Rta (replication and transcription activator) is primarily encoded by open reading frame 50 (ORF50), which is well conserved among gammaherpesviruses. EBV Rta and another viral protein, ZEBRA, function in a cooperative manner to reactivate the viral lytic cycle (2,5,19,27). Although ZEBRA plays a more prominent role in inducing EBV lytic replication (4, 10, 14), Rta alone can disrupt latency in some latently infected cell lines (19,27). KSHV Rta has been shown to be sufficient to reactivate the virus from latently infected B cells derived from KSHV-associated lymphomas (13,22). We have previously shown that MHV-68 Rta is also able to disrupt viral latency and drive viral lytic replication to completion in a latently MHV-68-infected B-cell lymphoma line (26). These studies indicate that Rta of gammaherpesviruses plays a conserved role in virus reactivation.