The genome of the rat cytomegalovirus (RCMV) English isolate (MuHV-8) differs significantly from the RCMV Maastricht isolate (MuHV-2) and other cytomegaloviruses (CMVs) in its size, base composition and genomic content. Analysis of the RCMV-Berlin isolate, MuHV-8, revealed that the two MuHV-8 isolates are highly similar in genome size and content, indicating that the smaller genome size (202946 bp) compared to other known CMVs was not the result of an accidental deletion during passage in tissue culture. Surprisingly, the proteins encoded in MuHV-8 shared more overall similarity with their orthologues from mouse CMV (MuHV-1) compared to their orthologues in rat CMV (MuHV-2). Phylogenetic analyses of conserved viral genes showed that the two MuHV-8 isolates are from the same species and represent a unique clade that is distinct from other rodent CMVs.

Hantaviruses are emerging zoonotic pathogens which cause hemorrhagic fever with renal syndrome, an immune-mediated pathogenesis is discussed. The aim of the present study was to investigate the role of TGF-β expression in acute hantavirus infection.

Infection of rats with RCMV serves as an important model to study human CMV-related diseases. Two prototype RCMV isolates, the English isolate of RCMV (RCMV-E) and the Maastricht isolate (RCMV-M) have been described in the literature that differ significantly from each other by genome size, restriction fragment length polymorphism, and genome content. According to genome size, the RCMV-M genome is similar to that of murine CMV whereas RCMV-E has a substantially smaller genome consisting of only 203 kbp. In addition, RCMV-E encodes several genes that are not part of the other rodent CMV genomes, which makes it a distinct virus. In this chapter, we will first highlight these particular genes and their impact on the immune system as well as on recent advances in the understanding of RCMV biology. In the second part, we will focus on the use of RCMV-M in studying vascular disease.

We identified Dobrava-Belgrade virus infection in Turkey (from a strain related to hantavirus strains from nearby countries) in a patient who had severe symptoms leading to panhypopituitarism, but no known risk for hantavirus. Our findings emphasize the need for increased awareness of hantaviruses in the region and assessment of symptomatic persons without known risk factors for infection.

The complete genome of the English isolate of rat cytomegalovirus (RCMV-E) was determined. RCMV-E has a 202,946-bp genome with noninverting repeats but without terminal repeats. Thus, it differs significantly in size and genomic arrangement from closely related rodent cytomegaloviruses (CMVs). To account for the differences between the rat CMV isolates of Maastricht and England, RCMV-E was classified as Murid herpesvirus 8 by the International Committee on Taxonomy of Viruses.

To investigate 2,017 cases of hantavirus disease in Germany, we compared 38 new patient-derived Puumala virus RNA sequences identified in 2010 with bank vole-derived small segment RNA sequences. The epidemic process was driven by outbreaks of 6 Puumala virus clades comprising strains of human and vole origin. Each clade corresponded to a different outbreak region.

The immediate-early 1 (IE1) and IE2 proteins encoded by the major immediate-early (MIE) transcription unit of cytomegaloviruses are thought to play key roles in the switch between latent-and lytic-cycle infection. Whilst IE2 is essential for triggering the lytic cycle, the exact roles of IE1 have not been resolved. An MIE-exon 4-deleted rat cytomegalovirus (Delta IE1) failed to synthesize the IE1 protein and did not disperse promyelocytic leukaemia bodies early post-infection, but was still capable of normal replication in fibroblast cell culture. However, Delta IE1 had a diminished ability to infect salivary glands persistently in vivo and to reactivate from spleen explant cultures ex vivo. Quantification of viral genomes in spleens of infected animals revealed a reduced amount of Delta IE1 virus produced during acute infection, suggesting a role for IE1 as a regulator in establishing a chronic or persistent infection, rather than in influencing the latency or reactivation processes more directly.

Cytomegaloviruses are known to encode several gene products that function to subvert MHC-dependent immune recognition. Here we characterize a rat cytomegalovirus (RCMV) C-type lectin-like (RCTL) gene product with homology to the Clr ligands for the NKR-P1 receptors. RCMV infection rapidly extinguished host Clr-b expression, thereby sensitizing infected cells to killing by natural killer (NK) cells. However, the RCTL protein functioned as a decoy ligand to protect infected cells from NK killing via direct interaction with the NKR-P1 B inhibitory receptor. In vivo, an RCTL mutant virus displayed diminished virulence in an NK-dependent and strain-specific manner, suggesting that host NKR-P1 polymorphisms have evolved to avert the viral decoy mechanism while maintaining Clr-b recognition to preserve self tolerance. These findings reveal a unique strategy adopted by cytomegaloviruses to evade MHC-independent self-nonself discrimination. The existence of lectin-like genes in several poxviruses suggests that this may represent a common theme for viral evasion of innate immunity.

(A) REF cells were infected with the indicated viruses (WT, ∆RCTL, REV), then RNA was extracted and cDNA prepared. Samples were normalized according to input cDNA, then subjected to real-time PCR analysis using primers and probes specific for the indicated target sequences (RCTL, rClr-b, rCLEC2D5; see Supplementary Table 2). *Values are plotted for the indicated target gene products normalized relative to host c-myc expression. Values plotted on the x-axis represent undetectable quantities; Ø, mock infections. (B) As in (A) except that WT- infected REF cells were pre-treated with cycloheximide (CHX) or phosphonoacetic acid (PAA) prior to infection. CHX results, 6h post-infection; PAA results, 9h post-infection.