Identification of Novel Rodent Herpesviruses, Including the First Gammaherpesvirus of Mus musculus

Abstract

Rodent herpesviruses such as murine cytomegalovirus (host, Mus musculus), rat cytomegalovirus (host, Rattus norvegicus), and murine gammaherpesvirus 68 (hosts, Apodemus species) are important tools for the experimental study of human herpesvirus diseases. However, alphaherpesviruses, roseoloviruses, and lymphocryptoviruses, as well as rhadinoviruses, that naturally infect Mus musculus (house mouse) and other Old World mice are unknown. To identify hitherto-unknown rodent-associated herpesviruses, we captured M. musculus, R. norvegicus, and 14 other rodent species in several locations in Germany, the United Kingdom, and Thailand. Samples of trigeminal ganglia, dorsal root ganglia, brains, spleens, and other organs, as well as blood, were analyzed with a degenerate panherpesvirus PCR targeting the DNA polymerase (DPOL) gene. Herpesvirus-positive samples were subjected to a second degenerate PCR targeting the glycoprotein B (gB) gene. The sequences located between the partial DPOL and gB sequences were amplified by long-distance PCR and sequenced, resulting in a contiguous sequence of approximately 3.5 kbp. By DPOL PCR, we detected 17 novel betaherpesviruses and 21 novel gammaherpesviruses but no alphaherpesvirus. Of these 38 novel herpesviruses, 14 were successfully analyzed by the complete bigenic approach. Most importantly, the first gammaherpesvirus of Mus musculus was discovered (Mus musculus rhadinovirus 1 [MmusRHV1]). This virus is a member of a novel group of rodent gammaherpesviruses, which is clearly distinct from murine herpesvirus 68-like rodent gammaherpesviruses. Multigenic phylogenetic analysis, using an 8-kbp locus, revealed that MmusRHV1 diverged from the other gammaherpesviruses soon after the evolutionary separation of EpsteinBarr virus-like lymphocryptoviruses from human herpesvirus 8-like rhadinoviruses and alcelaphine herpesvirus 1-like macaviruses.

Indigenous house mice dominate small mammal communities in northern Afghan military bases

“…As airlifts to Afghanistan were conducted from both areas (Cologne airport and Leipzig airport), animals from Western Germany and North Western Czech Republic (representing the Central European M. m. musculus population) were selected. The trapping of control animals for astrovirus and herpesvirus investigations at five sites in Germany and one site in the United Kingdom have been reported previously [13,17,18]. As no morphological vouchers could be preserved in this study, some preliminary species identifications were based on the photographic documentation and comparisons with museum specimens.…”

“…PCR amplification of the cytochrome b gene was conducted for each sample as described above to determine DNA amplificability. Amplification of the DPOL gene was conducted as described before [17]. Briefly, PCR was performed in nested format using a mixture of six degenerated/deoxyinosine substituted primers and delivering an expected Resulting PCR products were subjected to gel electrophoresis in a 3% agarose gel in 1× TAE buffer at 100 V for 45 min.…”

“…Sequencing reactions using the Big Dye v3.1 kit (Applied Biosystems) and DNA sequence analysis were performed as described above. Resulting nucleotide and in silico translated amino acid sequences were amended by sequences from further sites in Germany and the United Kingdom from a previous study as described therein [17] and a reference sequence (accession number AY854167). Alignments of viral nucleotide and amino acid sequences were conducted with BioEdit (version 7.2.5) and ClustalW [20].…”

Interferon, the Cell Cycle and Herpesvirus

“…Deletion mutant VZV virus infection of skin and T cells xenografts in vivo also indicated that ORF35 is a determinant of VZV virulence (Ito et al, 2005). It would be important to analyze the ORF20 mutant MHV-68 pathogenesis in its natural host, the wood mice (members of the genus Apodemus) (Ehlers et al, 2007), as a recent comparative analysis revealed that MHV-68 infection of BALB/c (M. musculus) and laboratory-bred wood mice are markedly different (Hughes et al, 2010). In conclusion, manipulation of the DNA damage response is a major target of herpesviruses, and one that in turn may determine a variety of significant outcomes to favor the virus, with cell cycle arrest and induction of IL-8 now identified.…”

Detection of Transcripts and an Infectious Dose of Murine Gammaherpesvirus 68 in Dermacentor reticulatus Ticks

“…Epidemiological surveys in the UK, Germany, France, and Peru found several other gammaherpesviruses in free-living rodents [3][4][5][6]. Although it has been documented that MHV-68 is mainly transmitted in the rodent population via intranasal routes and through body fluids, such as saliva, urine, tears, and breast milk, it is not yet fully understood how this virus spreads in nature.…”