The family Arteriviridae presently includes a single genus Arterivirus. This genus includes four species as the taxonomic homes for equine arteritis virus (EAV), lactate dehydrogenase-elevating virus (LDV), porcine respiratory and reproductive syndrome virus (PRRSV), and simian hemorrhagic fever virus (SHFV), respectively. A revision of this classification is urgently needed to accommodate the recent description of eleven highly divergent simian arteriviruses in diverse African nonhuman primates, one novel arterivirus in an African forest giant pouched rat, and a novel arterivirus in common brushtails in New Zealand. In addition, the current arterivirus nomenclature is not in accordance with the most recent version of the International Code of Virus Classification and Nomenclature. Here we outline an updated, amended, and improved arterivirus taxonomy based on current data. Taxon-specific sequence cut-offs are established relying on a newly established open reading frame 1b phylogeny and pairwise sequence comparison (PASC) of coding-complete arterivirus genomes. As a result, the current genus Arterivirus is replaced by five genera: Equartevirus (for EAV), Rodartevirus (LDV + PRRSV), Simartevirus (SHFV + simian arteriviruses), Nesartevirus (for the arterivirus from forest giant pouched rats), and Dipartevirus (common brushtail arterivirus). The current species Porcine reproductive and respiratory syndrome virus is divided into two species to accommodate the clear divergence of the European and American “types” of PRRSV, both of which now receive virus status. The current species Simian hemorrhagic fever virus is divided into nine species to accommodate the twelve known simian arteriviruses. Non-Latinized binomial species names are introduced to replace all current species names to clearly differentiate them from virus names, which remain largely unchanged.
43 SARS-CoV-2 pulmonary abnormalities in macaques Finch et al. 3 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing an 44 exponentially increasing number of coronavirus disease 19 (COVID-19) cases 45 globally. Prioritization of medical countermeasures for evaluation in randomized 46 clinical trials is critically hindered by the lack of COVID-19 animal models that 47 enable accurate, quantifiable, and reproducible measurement of COVID-19 48 pulmonary disease free from observer bias. We first used serial computed 49 tomography (CT) to demonstrate that bilateral intrabronchial instillation of SARS-50 CoV-2 into crab-eating macaques (Macaca fascicularis) results in mild-to-moderate 51 lung abnormalities qualitatively characteristic of subclinical or mild-to-moderate 52 COVID-19 (e.g., ground-glass opacities with or without reticulation, paving, or 53 alveolar consolidation, peri-bronchial thickening, linear opacities) at typical 54 locations (peripheral>central, posterior and dependent, bilateral, multi-lobar). We 55 then used positron emission tomography (PET) analysis to demonstrate increased 56 FDG uptake in the CT-defined lung abnormalities and regional lymph nodes. 57 PET/CT imaging findings appeared in all macaques as early as 2 days post-58 exposure, variably progressed, and subsequently resolved by 6-12 days post-59 exposure. Finally, we applied operator-independent, semi-automatic quantification 60 of the volume and radiodensity of CT abnormalities as a possible primary endpoint 61 for immediate and objective efficacy testing of candidate medical countermeasures. 62 63
Middle East respiratory syndrome coronavirus (MERS-CoV) presents an emerging threat to public health worldwide by causing severe respiratory disease in humans with high virulence and case fatality rate (about 35%) since 2012. Little is known about the pathogenesis and innate antiviral response in primary human monocyte-derived macrophages (MDMs) and dendritic cells (MDDCs) upon MERS-CoV infection. In this study, we assessed MERS-CoV replication as well as induction of inflammatory cytokines and chemokines in MDMs and immature and mature MDDCs. Immature MDDCs and MDMs were permissive for MERS-CoV infection, while mature MDDCs were not, with stimulation of proinflammatory cytokine and chemokine upregulation in MDMs, but not in MDDCs. To further evaluate the antiviral activity of well-defined drugs in primary antigen presenting cells (APCs), three compounds (chloroquine, chlorpromazine and toremifine), each with broad-spectrum antiviral activity in immortalized cell lines, were evaluated in MDMs and MDDCs to determine their antiviral effect on MERS-CoV infection. While chloroquine was not active in these primary cells, chlorpromazine showed strong anti-MERS-CoV activity, but it was associated with high cytotoxicity narrowing the potential window for drug utilization. Unlike in established cells, toremifene had marginal activity when tested in antigen presenting cells, with high apparent cytotoxicity, also limiting its potential as a therapeutic option. These results demonstrate the value of testing drugs in primary cells, in addition to established cell lines, before initiating preclinical or clinical studies for MERS treatment and the importance of carefully assessing cytotoxicity in drug screen assays. Furthermore, these studies also highlight the role of APCs in stimulating a robust protective immune response to MERS-CoV infection.
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