PMID- 33797313 OWN - NLM STAT- MEDLINE DCOM- 20211216 LR - 20211216 IS - 2150-5608 (Electronic) IS - 2150-5594 (Print) IS - 2150-5594 (Linking) VI - 12 IP - 1 DP - 2021 Dec TI - Attenuation of porcine deltacoronavirus disease severity by porcine reproductive and respiratory syndrome virus coinfection in a weaning pig model. PG - 1011-1021 LID - 10.1080/21505594.2021.1908742 [doi] AB - Porcine deltacoronavirus (PDCoV) is a potentially emerging zoonotic pathogen that causes severe diarrhea in young pigs, with a risk of fatal dehydration. Its pathogenicity on neonatal piglet has been previously reported, however, it is less known if the coinfection with immunosuppressive pathogens can influence PDCoV disease manifestation. Here, a coinfection model of PDCoV and porcine reproductive and respiratory syndrome virus (PRRSV), a global-spread immunosuppressive virus, was set to study their interaction. Weaning pigs in the coinfection group were intranasally inoculated with PRRSV NADC30-like virus and latterly orally inoculated with PDCoV at three day-post-inoculation (DPI). Unexpectedly, compared with pigs in the PDCoV single-infected group, the coinfected pigs did not show any obvious diarrhea, as PDCoV fecal shedding, average daily weight gain (ADWG), gross and microscopic lesions and PDCoV IHC scores consistently indicated that PRRSV coinfection lessened PDCoV caused diarrhea. Additionally, three proinflammatory cytokines TNF-alpha, IL-1 and IL-6, which can be secreted by PRRSV infected macrophages, were detected to be highly expressed at the intestine from both PRRSV infected groups. By adding to PDCoV-infected cells, these three cytokines were further confirmed to be able to inhibit the PDCoV replication post its cellular entry. Meanwhile, the inhibition effect of the supernatant from PRRSV-infected PAMs could be obviously blocked by the antagonist of these three cytokines. In conclusion, PRRSV coinfection increased TNF-alpha, IL-1, and IL-6 in the microenvironment of intestines, which inhibits the PDCoV proliferation, leading to lessened severity of diarrhea. The findings provide some new insight into the pathogenesis and replication regulation of PDCoV. FAU - Zhou, Xinrong AU - Zhou X AD - Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing, P.R. China. FAU - Ge, Xinna AU - Ge X AD - Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing, P.R. China. FAU - Zhang, Yongning AU - Zhang Y AD - Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing, P.R. China. FAU - Han, Jun AU - Han J AD - Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing, P.R. China. FAU - Guo, Xin AU - Guo X AD - Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing, P.R. China. FAU - Chen, Yanhong AU - Chen Y AD - Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing, P.R. China. FAU - Zhou, Lei AU - Zhou L AUID- ORCID: 0000-0002-8837-3965 AD - Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing, P.R. China. FAU - Yang, Hanchun AU - Yang H AD - Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing, P.R. China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Virulence JT - Virulence JID - 101531386 RN - 0 (Cytokines) RN - 0 (Interleukin-1) RN - 0 (Interleukin-6) RN - 0 (Tumor Necrosis Factor-alpha) RN - Porcine coronavirus HKU15 SB - IM MH - Animals MH - *Coinfection MH - Cytokines MH - *Deltacoronavirus MH - Diarrhea/veterinary MH - Interleukin-1 MH - Interleukin-6 MH - *Porcine respiratory and reproductive syndrome virus MH - Severity of Illness Index MH - Swine MH - *Swine Diseases/virology MH - Tumor Necrosis Factor-alpha MH - Weaning PMC - PMC8023240 OTO - NOTNLM OT - Porcine deltacoronavirus OT - coinfection OT - pathogenicity OT - porcine reproductive and respiratory syndrome virus OT - proinflammatory cytokines COIS- No potential conflict of interest was reported by the authors. EDAT- 2021/04/03 06:00 MHDA- 2021/12/17 06:00 PMCR- 2021/04/02 CRDT- 2021/04/02 12:13 PHST- 2021/04/02 12:13 [entrez] PHST- 2021/04/03 06:00 [pubmed] PHST- 2021/12/17 06:00 [medline] PHST- 2021/04/02 00:00 [pmc-release] AID - 1908742 [pii] AID - 10.1080/21505594.2021.1908742 [doi] PST - ppublish SO - Virulence. 2021 Dec;12(1):1011-1021. doi: 10.1080/21505594.2021.1908742.