The Gammaherpesvirus 68 Latency-Associated Nuclear Antigen Homolog Is Critical for the Establishment of Splenic Latency

Abstract

The gammaherpesviruses include the human pathogens Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV, or human herpesvirus 8). These viruses establish life-long infection of the host and are associated with a number of malignancies. To better understand gammaherpesvirus pathogenesis, we and others have studied infection of mice with murine gammaherpesvirus 68 (␥HV68, also referred to as MHV-68), a member of the ␥ 2 -herpesvirus family based on genome sequence (17).The pathogenesis of ␥HV68 has been reviewed recently (32,41). Briefly, ␥HV68 infection of inbred mice results in an acute, productive infection of multiple organs and a CD4 ϩ

Bovine herpesvirus 4 ORF73 is dispensable for virus growth in vitro, but is essential for virus persistence in vivo

“…Also, one cannot exclude that the deletion of the entire ORF73 could have disrupted neighbouring virus functions. Although the disruption of other virus functions could in theory have explained the phenotype observed for the ORF73 BoHV-4 recombinant, this phenotype was consistent with less dramatic mutations of MHV-68 ORF73 (Fowler et al, 2003;Moorman et al, 2003).…”

Latent herpesvirus infection arms NK cells

“…Our experiments examining the arming of NK cells, as well as previous experiments that uncovered heightened resistance against Listeria monocytogenes during herpesvirus latency, 18 made use of the latency-defective MuHV-4 mutant O73.stop. This virus replicates to normal 22,28 or near-normal levels 23 during acute infection but is severely defective in its ability to persist in the latent state. NK-cell activation is equivalent for wild-type MuHV-4 and O73.stop during acute infection.…”

“…22,23 O73.stop undergoes productive acute replication, elicits a normal humoral immune response (data not shown and Barton et al 18 ), and activates NK cells during acute infection indistinguishably from wild-type MuHV-4 (supplemental Figure 3). However, 28 days after infection with O73.stop, there was no increase in GzmB protein expression or degranulation by NK cells (Figures 1-2).…”

CD4+ T cells specific for a model latency‐associated antigen fail to control a gammaherpesvirus in vivo

“…MHV-68 also evades CD8 + T cells during episome maintenance. Its episome maintenance protein, ORF73 [32,33], lacks the glycine/alanine-rich motif of EBNA-1, but incorporates the same cis-acting inhibition of protein synthesis and degradation [5]. The MHV-68 ORF73 promoters are also remarkably analogous to those of EBNA-1, with one promoter just upstream of the ORF and two more that splice across multiple viral repeat units to generate an extensive 5 0 untranslated region [34].…”