Human, Nonhuman Primate, and Bat Cells Are Broadly Susceptible to Tibrovirus Particle Cell Entry

In 2012, the genome of a novel rhabdovirus, Bas-Congo virus (BASV), was discovered in the acute-phase serum of a Congolese patient with presumed viral hemorrhagic fever. In the absence of a replicating virus isolate, fulfilling Koch’s postulates to determine whether BASV is indeed a human virus and/or pathogen has been impossible. However, experiments with vesiculoviral particles pseudotyped with Bas-Congo glycoprotein suggested that BASV particles can enter cells from multiple animals, including humans. In 2015, genomes of two related viruses, Ekpoma virus 1 (EKV-1) and Ekpoma virus 2 (EKV-2), were detected in human sera in Nigeria. Isolates could not be obtained. Phylogenetic analyses led to the classification of BASV, EKV-1, and EKV-2 in the same genus, Tibrovirus, together with five biting midge-borne rhabdoviruses [i.e., Beatrice Hill virus (BHV), Bivens Arm virus (BAV), Coastal Plains virus (CPV), Sweetwater Branch virus (SWBV), and Tibrogargan virus (TIBV)] not known to infect humans. Using individual recombinant vesiculoviruses expressing the glycoproteins of all eight known tibroviruses and more than 75 cell lines representing different animal species, we demonstrate that the glycoproteins of all tibroviruses can mediate vesiculovirus particle entry into human, bat, nonhuman primate, cotton rat, boa constrictor, and Asian tiger mosquito cells. Using four of five isolated authentic tibroviruses (i.e., BAV, CPV, SWBV, and TIBV), our experiments indicate that many cell types may be partially resistant to tibrovirus replication after virion cell entry. Consequently, experimental data solely obtained from experiments using tibrovirus surrogate systems (e.g., vesiculoviral pseudotypes, recombinant vesiculoviruses) cannot be used to predict whether BASV, or any other tibrovirus, infects humans

Sequence variation, evolutionary constraint, and selection at the CD163 gene in pigs

Abstract Background In this work, we investigated sequence variation, evolutionary constraint, and selection at the CD163 gene in pigs. A functional CD163 protein is required for infection by porcine reproductive and respiratory syndrome virus, which is a serious pathogen with major impacts on pig production. Results We used targeted pooled sequencing of the exons of CD163 to detect sequence variants in 35,000 pigs of diverse genetic backgrounds and to search for potential stop-gain and frameshift indel variants. Then, we used whole-genome sequence data from three pig lines to calculate: a variant intolerance score that measures the tolerance of genes to protein coding variation; an estimate of selection on protein-coding variation over evolutionary time; and haplotype diversity statistics to detect recent selective sweeps during breeding. Conclusions Using a deep survey of sequence variation in the CD163 gene in domestic pigs, we found no potential knockout variants. The CD163 gene was moderately intolerant to variation and showed evidence of positive selection in the pig lineage, but no evidence of recent selective sweeps during breeding

Genome Sequence of Bivens Arm Virus, a Tibrovirus Belonging to the Species Tibrogargan virus (Mononegavirales: Rhabdoviridae).

The new rhabdoviral genus Tibrovirus currently has two members, Coastal Plains virus and Tibrogargan virus. Here, we report the coding-complete genome sequence of a putative member of this genus, Bivens Arm virus. A genomic comparison reveals Bivens Arm v

Receptor Usage of a Novel Bat Lineage C Betacoronavirus Reveals Evolution of Middle East Respiratory Syndrome-Related Coronavirus Spike Proteins for Human Dipeptidyl Peptidase 4 Binding

Although bats are known to harbor Middle East Respiratory Syndrome coronavirus (MERS-CoV)-related viruses, the role of bats in the evolutionary origin and pathway remains obscure. We identified a novel MERS-CoV-related betacoronavirus, Hp-BatCoV HKU25, from Chinese pipistrelle bats. Although it is closely related to MERS-CoV in most genome regions, its spike protein occupies a phylogenetic position between that of Ty-BatCoV HKU4 and Pi-BatCoV HKU5. Because Ty-BatCoV HKU4 but not Pi-BatCoV HKU5 can use the MERS-CoV receptor human dipeptidyl peptidase 4 (hDPP4) for cell entry, we tested the ability of Hp-BatCoV HKU25 to bind and use hDPP4. The HKU25-receptor binding domain (RBD) can bind to hDPP4 protein and hDPP4-expressing cells, but it does so with lower efficiency than that of MERS-RBD. Pseudovirus assays showed that HKU25-spike can use hDPP4 for entry to hDPP4-expressing cells, although with lower efficiency than that of MERS-spike and HKU4-spike. Our findings support a bat origin of MERS-CoV and suggest that bat CoV spike proteins may have evolved in a stepwise manner for binding to hDPP4

Taxonomy of the order Mononegavirales: update 2018

In 2018, the order Mononegavirales was expanded by inclusion of 1 new genus and 12 novel species. This article presents the updated taxonomy of the order Mononegavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV) and summarizes additional taxonomic proposals that may affect the order in the near future

Monocyte-lymphocyte cross-communication via soluble CD163 directly links innate immune system activation and adaptive immune system suppression following ischemic stroke

Abstract CD163 is a scavenger receptor expressed on innate immune cell populations which can be shed from the plasma membrane via the metalloprotease ADAM17 to generate a soluble peptide with lympho-inhibitory properties. The purpose of this study was to investigate CD163 as a possible effector of stroke-induced adaptive immune system suppression. Liquid biopsies were collected from ischemic stroke patients (n = 39), neurologically asymptomatic controls (n = 20), and stroke mimics (n = 20) within 24 hours of symptom onset. Peripheral blood ADAM17 activity and soluble CD163 levels were elevated in stroke patients relative to non-stroke control groups, and negatively associated with post-stroke lymphocyte counts. Subsequent in vitro experiments suggested that this stroke-induced elevation in circulating soluble CD163 likely originates from activated monocytic cells, as serum from stroke patients stimulated ADAM17-dependant CD163 shedding from healthy donor-derived monocytes. Additional in vitro experiments demonstrated that stroke-induced elevations in circulating soluble CD163 can elicit direct suppressive effects on the adaptive immune system, as serum from stroke patients inhibited the proliferation of healthy donor-derived lymphocytes, an effect which was attenuated following serum CD163 depletion. Collectively, these observations provide novel evidence that the innate immune system employs protective mechanisms aimed at mitigating the risk of post-stroke autoimmune complications driven by adaptive immune system overactivation, and that CD163 is key mediator of this phenomenon