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We isolated Venezuelan equine encephalitis virus (VEEV) subtype IE phylogenetically related to Gulf Coast strains in a spider monkey (Ateles geoffroyi) released from a rescue center in Guatemala. Serologic testing of 118 monkeys indicated no additional VEEV infections. Infection of a primate warrants intensified surveillance of VEEV transmission cycles in North America.

Canine circoviruses (CanineCV’s), belonging to the genus Circovirus of the Circoviridae family, were detected by next generation sequencing in samples from Thai dogs with respiratory symptoms. Genetic characterization and phylogenetic analysis of nearly complete CanineCV genomes suggested that natural recombination had occurred among different lineages of CanineCV’s. Similarity plot and bootscaning analyses indicated that American and Chinese viruses had served as major and minor parental viruses, respectively. Positions of recombination breakpoints were estimated using maximum-likelihood frameworks with statistical significant testing. The putative recombination event was located in the Replicase gene, intersecting with open reading frame-3. Analysis of nucleotide changes confirmed the origin of the recombination event. This is the first description of naturally occurring recombinant CanineCV’s that have resulted in the circulation of newly emerging CanineCV lineages.

Community protective immunity can affect RNA virus evolution by selecting for new antigenic variants on the scale of years, exemplified by the need of annual evaluation of influenza vaccines. The extent to which this process termed antigenic drift affects coronaviruses remains unknown. Alike the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), seasonal human coronaviruses (HCoV) likely emerged from animal reservoirs as new human pathogens in the past. We therefore analyzed the long-term evolutionary dynamics of the ubiquitous HCoV-229E and HCoV-OC43 in comparison with human influenza A virus (IAV) subtype H3N2. We focus on viral glycoprotein genes that mediate viral entry into cells and are major targets of host neutralizing antibody responses. Maximum likelihood and Bayesian phylogenies of publicly available gene datasets representing about three decades of HCoV and IAV evolution showed that all viruses had similar ladder-like tree shapes compatible with antigenic drift, supported by different tree shape statistics. Evolutionary rates inferred in a Bayesian framework were 6.5 × 10−4 (95% highest posterior density (HPD), 5.4–7.5 × 10−4) substitutions per site per year (s/s/y) for HCoV-229E spike (S) genes and 5.7 × 10−4 (95% HPD, 5–6.5 × 10−4) s/s/y for HCoV-OC43 S genes, which were about fourfold lower than the 2.5 × 10−3 (95% HPD, 2.3–2.7 × 10−3) s/s/y rate for IAV hemagglutinin (HA) genes. Coronavirus S genes accumulated about threefold less (P < 0.001) non-synonymous mutations (dN) over time than IAV HA genes. In both IAV and HCoV, the average rate of dN within the receptor binding domains (RBD) was about fivefold higher (P < 0.0001) than in other glycoprotein gene regions. Similarly, most sites showing evidence for positive selection occurred within the RBD (HCoV-229E, 6/14 sites, P < 0.05; HCoV-OC43, 23/38 sites, P < 0.01; IAV, 13/15 sites, P = 0.08). In sum, the evolutionary dynamics of HCoV and IAV showed several similarities, yet amino acid changes potentially representing antigenic drift occurred on a lower scale in endemic HCoV compared to IAV. It seems likely that pandemic SARS-CoV-2 evolution will bear similarities with IAV evolution including accumulation of adaptive changes in the RBD, requiring vaccines to be updated regularly, whereas higher SARS-CoV-2 evolutionary stability resembling endemic HCoV can be expected in the post-pandemic stage.

Major depressive disorder (MDD) is a mood disorder of multifactorial origin affecting millions of people worldwide. The alarming estimated rates of prevalence and relapse make it a global public health concern. Moreover, the current setback of available antidepressants in the clinical setting is discouraging. Therefore, efforts to eradicate depression should be directed towards understanding the pathomechanisms involved in the hope of finding cost-effective treatment alternatives. The pathophysiology of MDD comprises the breakdown of different pathways, including the hypothalamus-pituitary-adrenal (HPA) axis, the glutamatergic system, and monoaminergic neurotransmission, affecting cognition and emotional behavior. Inflammatory cytokines have been postulated to be the possible link and culprit in the disruption of these systems. In addition, evidence from different studies suggests that impairment of glial functions appears to be a major contributor as well. Thus, the intricate role between glia, namely microglia and astrocytes, and the central nervous system's (CNSs) immune response is briefly discussed, highlighting the kynurenine pathway as a pivotal player. Moreover, evaluations of different treatment strategies targeting the inflammatory response are considered. The immuno-modulatory properties of vitamin D receptor (VDR) suggest that vitamin D is an attractive and plausible candidate in spite of controversial findings. Further research investigating the role of VDR in mood disorders is warranted.

Pestiviruses typically infect members of the order Artiodactyla, including ruminants and pigs, although putative rat and bat pestiviruses have also been described. In the present study, we identified and characterized an evolutionary divergent pestivirus in the toothed whale species, harbour porpoise (Phocoena phocoena). We tentatively named the virus Phocoena pestivirus (PhoPeV). PhoPeV displays a typical pestivirus genome organization except for the unique absence of N pro , an N-terminal autoprotease that targets the innate host immune response. Evolutionary evidence indicates that PhoPeV emerged following an interspecies transmission event from an ancestral pestivirus that expressed N pro . We show that 9% (n = 10) of stranded porpoises from the Dutch North Sea coast (n = 112) were positive for PhoPeV and they displayed a systemic infection reminiscent of non-cytopathogenic persistent pestivirus infection. The identification of PhoPeV extends the host range of pestiviruses to cetaceans (dolphins, whales, porpoises), which are considered to have evolved from artiodactyls (even-toed ungulates). Elucidation of the pathophysiology of PhoPeV infection and N pro unique absence will add to our understanding of molecular mechanisms governing pestivirus pathogenesis.

Canine morbillivirus (canine distemper virus; CDV) is a worldwide distributed morbillivirus that causes sporadic cases and recurrent epizootics among an increasing number of wild, feral, and domestic animal species. We investigated the evolutionary history of CDV strains involved in the 1988 Lake Baikal (CDVPS88) and the 2000 Caspian Sea (CDVPC00) seal die-offs by recovery of full-length sequences from archived material using next-generation sequencing. Bayesian phylogenetic analyses indicated that CDVPC00 constitutes a novel strain in a separate clade (tentatively termed “Caspian”) from the America-1 clade, which is comprised of older vaccine strains. The America-1/Caspian monophyletic group is positioned most basally with respect to other clades and is estimated to have separated from other CDV clades around 1832. Our results indicate that CDVPC00 recovered from the epizootic in the Caspian Sea in 2000 belongs to a previously undetected novel clade and constitutes the most ancestral wild-type CDV clade.

Skunk amdoparvovirus (Carnivore amdoparvovirus 4, SKAV) is closely related to Aleutian mink disease virus (AMDV) and circulates primarily in striped skunks (Mephitis mephitis) in North America. SKAV poses a threat to mustelid species due to reported isolated infections of captive American mink (Neovison vison) in British Columbia, Canada. We detected SKAV in a captive striped skunk in a German zoo by metagenomic sequencing. The pathological findings are dominated by lymphoplasmacellular inflammation and reveal similarities to its relative Carnivore amdoparvovirus 1, the causative agent of Aleutian mink disease. Phylogenetic analysis of the whole genome demonstrated 94.80% nucleotide sequence identity to a sequence from Ontario, Canada. This study is the first case description of a SKAV infection outside of North America.

Cetacean morbillivirus (CeMV) has emerged as the pathogen that poses the greatest risk of triggering epizootics in cetacean populations worldwide, and has a high propensity for interspecies transmission, including sporadic infection of seals. In this study, we investigated the evolutionary history of CeMV by deep sequencing wild-type viruses from tissue samples representing cetacean species with different spatiotemporal origins. Bayesian phylogeographic analysis generated an estimated evolutionary rate of 2.34 × 10 −4 nucleotide substitutions/site/year and showed that CeMV evolutionary dynamics are neither host-restricted nor location-restricted. Moreover, the dolphin morbillivirus strain of CeMV has undergone purifying selection without evidence of species-specific mutations. Cell-to-cell fusion and growth kinetics assays demonstrated that CeMV can use both dolphin and seal CD150 as a cellular receptor. Thus, it appears that CeMV can readily spread among multiple cetacean populations and may pose an additional spillover risk to seals.

Background Rabbit hemorrhagic disease virus (RHDV, Lagovirus europeus GI.1) induces a contagious and highly lethal hemorrhagic disease in rabbits. In 2010 a new genotype of lagovirus (GI.2), emerged in Europe, infecting wild and domestic population of rabbits and hares. Case presentation We describe the infection with a GI.2 strain, “Bremerhaven-17”, in captive mountain hares ( Lepus timidus ) in a zoo facility in Germany. Postmortem examination revealed RHD-like lesions including necrotizing hepatitis. RT-qPCR and AG-ELISA confirmed presence of GI.2. Recombination and phylogenetic analysis grouped the identified strain with other GI.2 strains, sharing nucleotide identity of 91–99%. Conclusion Our findings confirm that mountain hares are susceptible to GI.2 infection, due to a past recombination event facilitating virus spillover from sympatric rabbits .

Canine kobuvirus (CaKV) is a globally distributed pathogen of dogs and is predominantly associated with infection of the gastrointestinal tract. However, an etiological link to enteric disease has not been established since CaKV has been identified in both asymptomatic dogs and animals with diarrheic symptoms. In this study, an extraintestinal CaKV infection was detected by next-generation sequencing in a fox (Vulpes vulpes) in Germany concomitant with a canine distemper virus (canine morbillivirus; CDV) co-infection. Phylogenetic analysis of the complete coding region sequence showed that this strain was most closely related to a CaKV strain detected in a dog in the United Kingdom in 2008. The tissue and cellular tropism of CaKV was characterized by the detection of viral antigens and RNA. CaKV RNA was detected by in situ hybridization in different tissues, including epithelial cells of the stomach and ependymal cells in the brain. The use of a new RT-qPCR assay for CaKV confirmed the systemic distribution of CaKV with viral RNA also detected in the lymph nodes, bladder, trachea, and brain. The detection of a CDV infection in this fox suggests that immunosuppression should be further investigated as a contributing factor to the enhanced extraintestinal spread of CaKV.