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New Parvoviruses and Picornavirus in Tissues and Feces of Foals with Interstitial Pneumonia.

ABSTRACT: Six foals with interstitial pneumonia of undetermined etiology from Southern California were analyzed by viral metagenomics. Spleen, lung, and colon content samples obtained during necropsy from each animal were pooled, and nucleic acids from virus-like particles enriched for deep sequencing. The recently described equine copiparvovirus named eqcopivirus, as well as three previously uncharacterized viruses, were identified. The complete ORFs genomes of two closely related protoparvoviruses, and of a bocaparvovirus, plus the partial genome of a picornavirus were assembled. The parvoviruses were classified as members of new ungulate protoparvovirus and bocaparvovirus species in the Parvoviridae family. The picornavirus was classified as a new species in the Salivirus genus of the Picornaviridae family. Spleen, lung, and colon content samples from each foal were then tested for these viral genomes by nested PCR and RT-PCR. When present, parvoviruses were detected in both feces and spleen. The picornavirus, protoparvovirus, and eqcopivirus genomes were detected in the lungs of one animal each. Three foals were co-infected with the picornavirus and either a protoparvovirus, bocaparvovirus, or eqcopivirus. Two other foals were infected with a protoparvovirus only. No viral infection was detected in one animal. The complete ORFs of the first equine protoparvoviruses and bocaparvovirus, the partial ORF of the third equine picornavirus, and their detection in tissues of foals with interstitial pneumonia are described here. Testing the involvement of these viruses in fatal interstitial pneumonia or other equine diseases will require larger epidemiological and/or inoculation studies.

SUBMITTER: Altan E

PROVIDER: S-EPMC8402702 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PURPOSE:To conduct a meta-analysis to determine specific computed tomography (CT) patterns and clinical features that discriminate between nonspecific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP). MATERIALS AND METHODS:The PubMed/Medline and Embase databases were searched for studies describing the radiological patterns of UIP and NSIP in chest CT images. Only studies involving histologically confirmed diagnoses and a consensus diagnosis by an interstitial lung disease (ILD) board were included in this analysis. The radiological patterns and patient demographics were extracted from suitable articles. We used random-effects meta-analysis by DerSimonian & Laird and calculated pooled odds ratios for binary data and pooled mean differences for continuous data. RESULTS:Of the 794 search results, 33 articles describing 2,318 patients met the inclusion criteria. Twelve of these studies included both NSIP (338 patients) and UIP (447 patients). NSIP-patients were significantly younger (NSIP: median age 54.8 years, UIP: 59.7 years; mean difference (MD) -4.4; p = 0.001; 95% CI: -6.97 to -1.77), less often male (NSIP: median 52.8%, UIP: 73.6%; pooled odds ratio (OR) 0.32; p<0.001; 95% CI: 0.17 to 0.60), and less often smokers (NSIP: median 55.1%, UIP: 73.9%; OR 0.42; p = 0.005; 95% CI: 0.23 to 0.77) than patients with UIP. The CT findings from patients with NSIP revealed significantly lower levels of the honeycombing pattern (NSIP: median 28.9%, UIP: 73.4%; OR 0.07; p<0.001; 95% CI: 0.02 to 0.30) with less peripheral predominance (NSIP: median 41.8%, UIP: 83.3%; OR 0.21; p<0.001; 95% CI: 0.11 to 0.38) and more subpleural sparing (NSIP: median 40.7%, UIP: 4.3%; OR 16.3; p = 0.005; 95% CI: 2.28 to 117). CONCLUSION:Honeycombing with a peripheral predominance was significantly associated with a diagnosis of UIP. The NSIP pattern showed more subpleural sparing. The UIP pattern was predominantly observed in elderly males with a history of smoking, whereas NSIP occurred in a younger patient population.

Project description:Few drugs targeting picornaviruses are available, making the discovery of antivirals a high priority. Here, we identified and characterized three compounds from a library of kinase inhibitors that block replication of poliovirus, coxsackievirus B3, and encephalomyocarditis virus. Using an in vitro translation-replication system, we showed that these drugs inhibit different stages of the poliovirus life cycle. A4(1) inhibited both the formation and functioning of the replication complexes, while E5(1) and E7(2) were most effective during the formation but not the functioning step. Neither of the compounds significantly inhibited VPg uridylylation. Poliovirus resistant to E7(2) had a G5318A mutation in the 3A protein. This mutation was previously found to confer resistance to enviroxime-like compounds, which target a phosphatidylinositol 4-kinase III? (PI4KIII?)-dependent step in viral replication. Analysis of host protein recruitment showed that E7(2) reduced the amount of GBF1 on the replication complexes; however, the level of PI4KIII? remained intact. E7(2) as well as another enviroxime-like compound, GW5074, interfered with viral polyprotein processing affecting both 3C- and 2A-dependent cleavages, and the resistant G5318A mutation partially rescued this defect. Moreover, E7(2) induced abnormal recruitment to membranes of the viral proteins; thus, enviroxime-like compounds likely severely compromise the interaction of the viral polyprotein with membranes. A4(1) demonstrated partial protection from paralysis in a murine model of poliomyelitis. Multiple attempts to isolate resistant mutants in the presence of A4(1) or E5(1) were unsuccessful, showing that effective broad-spectrum antivirals could be developed on the basis of these compounds.Diverse picornaviruses can trigger multiple human maladies, yet currently, only hepatitis A virus and poliovirus can be controlled with vaccination. The development of antipicornavirus therapeutics is also facing significant difficulties because these viruses readily generate resistance to compounds targeting either viral or cellular factors. Here, we describe three novel compounds that effectively block replication of distantly related picornaviruses with minimal toxicity to cells. The compounds prevent viral RNA replication after the synthesis of the uridylylated VPg primer. Importantly, two of the inhibitors are strongly refractory to the emergence of resistant mutants, making them promising candidates for further broad-spectrum therapeutic development. Evaluation of one of the compounds in an in vivo model of poliomyelitis demonstrated partial protection from the onset of paralysis.

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New Parvoviruses and Picornavirus in Tissues and Feces of Foals with Interstitial Pneumonia.

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