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Erk5 is a mitogen-activated protein kinase, the biological role of which is largely undefined. Therefore, we deleted the erk5 gene in mice to assess its function in vivo. Inactivation of the erk5 gene resulted in defective blood-vessel and cardiac development leading to embryonic lethality around embryonic days 9.5-10.5. Cardiac development was retarded largely, and the heart failed to undergo normal looping. Endothelial cells that line the developing myocardium of erk5؊͞؊ embryos displayed a disorganized, rounded morphology. Vasculogenesis occurred, but extraembryonic and embryonic blood vessels were disorganized and failed to mature. Furthermore, the investment of embryonic blood vessels with smooth muscle cells was attenuated. Together, these data define an essential role for Erk5 in cardiovascular development. Moreover, the inability of Erk5-deficient mice to form a complex vasculature suggests that Erk5 may play an important role in controlling angiogenesis.

Marek's disease virus (MDV) causes a general malaise in chickens that is mostly characterized by the development of lymphoblastoid tumors in multiple organs. The use of bacterial artificial chromosomes (BACs) for cloning and manipulation of the MDV genome has facilitated characterization of specific genes and genomic regions. The development of most MDV BACs, including pRB-1B-5, derived from a very virulent MDV strain, involved replacement of the U S 2 gene with mini-F vector sequences. However, when reconstituted viruses based on pRB-1B were used in pathogenicity studies, it was discovered that contact chickens housed together with experimentally infected chickens did not contract Marek's disease (MD), indicating a lack of horizontal transmission. Staining of feather follicle epithelial cells in the skins of infected chickens showed that virus was present but was unable to be released and/or infect susceptible chickens. Restoration of U S 2 and removal of mini-F sequences within viral RB-1B did not alter this characteristic, although in vivo viremia levels were increased significantly. Sequence analyses of pRB-1B revealed that the U L 13, U L 44, and U S 6 genes encoding the U L 13 serine/threonine protein kinase, glycoprotein C (gC), and gD, respectively, harbored frameshift mutations. These mutations were repaired individually, or in combination, using two-step Red mutagenesis. Reconstituted viruses were tested for replication, MD incidence, and their abilities to horizontally spread to contact chickens. The experiments clearly showed that U S 2, U L 13, and gC in combination are essential for horizontal transmission of MDV and that none of the genes alone is able to restore this phenotype.Marek's disease virus (MDV), also known as Gallid herpesvirus 2, causes Marek's disease (MD), a lymphoproliferative disease in chickens characterized by the development of tumors in the viscera and other organs. The pathogenesis of infection with MDV can be divided into four phases (4). In the first phase, between 3 and 6 days postinfection (p.i.), the primary target cells of infection are bursa-derived (B) lymphocytes. Infection of activated CD4 ϩ thymus-derived (T) lymphocytes follows in the second phase. During the second phase, viral replication typically decreases and a latent infection is established between 5 and 10 days p.i. in activated CD4 ϩ T lymphocytes. The third phase is characterized by reactivation of MDV replication between 14 and 21 days p.i. and infection of feather follicle epithelium (FFE) cells. After the third phase, virus is shed from the chicken in dried FFE cells, and clinical MD symptoms and lymphomas may develop depending on the genetic susceptibility of the chickens and the virulence of the virus strain.The MDV genome consists of the unique short (U S ) and long (U L ) regions, flanked by the inverted repeat long (IR L ) and short (IR S ) regions, and the terminal repeat long (TR L ) and short (TR S ) regions. Through manipulation of the MDV genome using multiple approaches, specific genes or re...

Members of the family Herpesviridae have enveloped, spherical virions with characteristic complex structures consisting of symmetrical and non-symmetrical components. The linear, double-stranded DNA genomes of 125–241 kbp contain 70–170 genes, of which 43 have been inherited from an ancestral herpesvirus. In general, herpesviruses have coevolved with and are highly adapted to their hosts, which comprise many mammalian, avian and reptilian species. Following primary infection, they are able to establish lifelong latent infection, during which there is limited viral gene expression. Severe disease is usually observed only in the foetus, the very young, the immunocompromised or following infection of an alternative host. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Herpesviridae, which is available at ictv.global/report/herpesviridae.