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PDZK1 upregulates nitric oxide production through the PI3K/ERK2 pathway to inhibit porcine circovirus type 2 replication.
- Source :
-
Veterinary Microbiology . Sep2022, Vol. 272, pN.PAG-N.PAG. 1p. - Publication Year :
- 2022
-
Abstract
- Porcine circovirus type 2 (PCV2) is the causative agent of porcine circovirus-associated disease. Changes in host cell gene expression are induced by PCV2 infection. Here, we showed that porcine PDZ Domain-Containing 1 (PDZK1) expression was enhanced during PCV2 infection and that overexpression of PDZK1 inhibited the expression of PCV2 Cap protein. PCV2 genomic DNA copy number and viral titers were decreased in PDZK1-overexpressing PK-15B6 cells. PDZK1 knockdown enhanced the replication of PCV2. Overexpression of PDZK1 activated the phosphoinositide 3-kinase (PI3K)/ERK2 signaling pathway to enhance nitric oxide (NO) levels, while PDZK1 knockdown had the opposite effects. A PI3K inhibitor (LY294002) and a NO synthase inhibitor (L -NAME hydrochloride) decreased the activity of PDZK1 in restricting PCV2 replication. ERK2 knockdown enhanced the proliferation of PCV2 by decreasing levels of NO. Levels of interleukin (IL)− 4 mRNA were reduced in PDZK1 knockdown and ERK2 knockdown PK-15B6 cells. Increased IL-4 mRNA levels were unable to decrease NO production in PDZK1-overexpressing cells. Thus, we conclude that PDZK1 affected PCV2 replication by regulating NO production via PI3K/ERK2 signaling. PDZK1 affected IL-4 expression through the PI3K/ERK2 pathway, but PDZK1 modulation of PCV2 replication occurred independently of IL-4. Our results contribute to understanding the biological functions of PDZK1 and provide a theoretical basis for the pathogenic mechanisms of PCV2. • Porcine PDZK1 expression was enhanced in PK-15B6 cells infected with PCV2. • Overexpression of PDZK1 resulted in increased NO production and inhibition of PCV2 replication via PI3K/ERK2 signaling. • Knockout of PDZK1 suppressed NO production to accelerate PCV2 replication by inhibiting PI3K/ERK2 signaling. • PDZK1 altered the expression of cytokines in PCV2-infected cells. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03781135
- Volume :
- 272
- Database :
- Academic Search Index
- Journal :
- Veterinary Microbiology
- Publication Type :
- Academic Journal
- Accession number :
- 158402691
- Full Text :
- https://doi.org/10.1016/j.vetmic.2022.109514