RESUMEN

CCCH-type zinc figure proteins (ZFP) are small cellular proteins that are structurally maintained by zinc ions. Zinc ions coordinate the protein structure in a tetrahedral geometry by binding to cystine-cystine or cysteines-histidine amino acids. ZFP's unique structure enables it to interact with a wide variety of molecules including RNA; thus, ZFP modulates several cellular processes including the host immune response and virus replication. CCCH-type ZFPs have shown their antiviral efficacy against several DNA and RNA viruses. However, their role in the human coronavirus is little explored. We hypothesized that ZFP36L1 also suppresses the human coronavirus. To test our hypothesis, we used OC43 human coronavirus (HCoV) strain in our study. We overexpressed and knockdown ZFP36L1 in HCT-8 cells using lentivirus transduction. Wild type, ZFP36L1 overexpressed, and ZFP36L1 knockdown cells were each infected with HCoV-OC43, and the virus titer in each cell line was measured over 96 hours post-infection (p.i.). Our results show that HCoV-OC43 replication was significantly reduced with ZFP36L1 overexpression while ZFP36L1 knockdown significantly enhanced virus replication. ZFP36L1 knockdown HCT-8 cells started producing infectious virus at 48 hours p.i. which was an earlier timepoint as compared to wild -type and ZFP36L1 overexpressed cells. Wild-type and ZFP36L1 overexpressed HCT-8 cells started producing infectious virus at 72 hours p.i. Overall, the current study showed that overexpression of ZFP36L1 suppressed human coronavirus (OC43) production.

Asunto(s)

Coronavirus Humano OC43 , Humanos , Coronavirus Humano OC43/genética , Cistina , Línea Celular , Replicación Viral/genética , Factor 1 de Respuesta al Butirato , Tristetraprolina

RESUMEN

Immunoglobulin A (IgA) is one of the important and most abundant immunoglobulins which neutralize invading pathogens at mucosal sites. Gut microbial community and their metabolites which are responsible for higher IgA are poorly known. The current study was carried out to determine those microbial community and their metabolites. Twenty-two healthy, 26 days wean piglets were used in the study. After 10 days of weaning, piglets were divided into two groups. Group 1 with significantly higher fecal IgA while group 2 with significantly lower IgA concentrations from each other. Both groups were analyzed for the fecal inflammatory cytokine, fecal microbial community using 16S ribosomal sequencing, and microbial metabolites using GC-MS. Results showed that Firmicutes and Bacteroidetes constituted 90.56% of the microbiome population in the fecal matter of pigs with higher IgA concentration while pigs with lower fecal IgA had Firmicutes and Bacteroidetes abundance as of 95.56%. Pigs with higher IgA had significantly higher Bacteroidota and Desulfobacterota populations, while significantly lower Firmicutes and Firmicutes/ Bacteroidota ratio (p <0.05). Roughly at the species level, animals with higher fecal IgA concentration had significantly higher bacteria which are associated with gut inflammation and infectious such Prevotella spp and Lachnospiraceae AC2044. Pigs with higher IgA had comparatively lower short-chain fatty acid (SCFA) such as acetic acid, butyric, formic acid, isovaleric acid, and propionic acid which has been associated with gut immune tolerance and immune homeostasis.