Abstract
Alcelaphine herpesvirus 1 (AlHV-1) is a gammaherpesvirus that is carried asymptomatically by wildebeest. Upon cross-species transmission to other ruminants, including domestic cattle, AlHV-1 induces malignant catarrhal fever (MCF), which is a fatal lymphoproliferative disease resulting from proliferation and uncontrolled activation of latently infected CD8+ T cells. Two laboratory strains of AlHV-1 are used commonly in research: C500, which is pathogenic, and WC11, which has been attenuated by long-term maintenance in cell culture. The published genome sequence of a WC11 seed stock from a German laboratory revealed the deletion of two major regions. The sequence of a WC11 seed stock used in our laboratory also bears these deletions and, in addition, the duplication of an internal sequence in the terminal region. The larger of the two deletions has resulted in the absence of gene A7 and a large portion of gene A8. These genes are positional orthologs of the Epstein-Barr virus genes encoding envelope glycoproteins gp42 and gp350, respectively, which are involved in viral propagation and switching of cell tropism. To investigate the degree to which the absence of A7 and A8 participates in WC11 attenuation, recombinant viruses lacking these individual functions were generated in C500. Using bovine nasal turbinate and embryonic lung cell lines, increased cell-free viral propagation and impaired syncytia formation were observed in the absence of A7, whereas cell-free viral spread was inhibited in the absence of A8. Therefore, A7 appears to be involved in cell-to-cell viral spread, and A8 in viral cell-free propagation. Finally, infection of rabbits with either mutant did not induce the signs of MCF or the expansion of infected CD8+ T cells. These results demonstrate that A7 and A8 are both essential for regulating viral spread and suggest that AlHV-1 requires both genes to efficiently spread in vivo and reach CD8+ T lymphocytes and induce MCF.
Highlights
Gammaherpesvirus infection results in lifelong viral persistence in the natural host through the establishment of latency, whereas reactivation from latency is responsible for transmission from one host to another and viral persistence at the population level
Gammaherpesvirus entry into immune cells can result in latent infection which is associated with viral persistence and severe lymphoproliferative diseases
Alcelaphine herpesvirus 1 (AlHV-1) is a gammaherpesvirus carried by wildebeests without causing any clinical sign but induces malignant catarrhal fever (MCF) upon transmission to several species of ruminants including cattle
Summary
Gammaherpesvirus infection results in lifelong viral persistence in the natural host through the establishment of latency, whereas reactivation from latency is responsible for transmission from one host to another and viral persistence at the population level. Primary acute gammaherpesvirus infection is usually asymptomatic, but, under specific circumstances, latent persistence can cause the development of severe proliferative diseases and cancers [1]. Most wildebeest naturally carry AlHV-1 infection, and, the virus establishes persistent infection in this species, wildebeest do not develop any clinical sign [11]. Upon transmission to related species, such as members of the subfamily Bovinae (including domesticated cattle), AlHV-1 can induce MCF, which is an acute, sporadic and fatal pan-systemic lymphoproliferative disease. MCF has been reported throughout the world in game farms or zoological collections in which mixed ruminant species including wildebeest are kept [15]
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