Zebrafish pten Genes Play Relevant but Distinct Roles in Antiviral Immunity

Abstract

The PTEN (phosphatase and TENsin homolog on chromosome 10) gene encodes a bifunctional phosphatase that acts as a tumor suppressor. However, PTEN has been implicated in different immune processes, including autophagy, inflammation, regulation of natural killer (NK) cell cytolytic activity and type I interferon responses. Unlike mammals, zebrafish possess two pten genes (ptena and ptenb). This study explores the involvement of both zebrafish pten genes in antiviral defense. Although ptena−/− and ptenb−/− larvae were more susceptible to Spring viremia of carp virus (SVCV), the viral replication rate was lower in the mutant larvae than in the wild-type larvae. We observed that both mutant lines showed alterations in the transcription of numerous genes, including those related to the type I interferon (IFN) system, cytolytic activity, autophagy and inflammation, and some of these genes were regulated in opposite ways depending on which pten gene was mutated. Even though the lower replication rate of SVCV could be associated with impaired autophagy in the mutant lines, the higher mortality observed in the ptena−/− and ptenb−/− larvae does not seem to be associated with an uncontrolled inflammatory response.

Tissue distribution and developmental changes of PTEN in the immune organs of chicken and effect of IBDV infection on it

“…In the present study, the PTEN mRNA level in the bursa was downregulated after chickens were infected with IBDV. This downregulation was also observed in the studies of Spring viremia of carp virus ( SVCV )-infected zebrafish model and HCV core protein-transfected HepG2 cell model ( Zhang et al., 2014 ; Pereiro et al., 2020 ). Subsequently, the antiviral function of PTEN in SVCV-infected zebrafish models and HCV-infected Huh-7.5 cell model was confirmed through PTEN overexpression ( Wu et al., 2017 ; Pereiro et al., 2020 ).…”

“…This downregulation was also observed in the studies of Spring viremia of carp virus ( SVCV )-infected zebrafish model and HCV core protein-transfected HepG2 cell model ( Zhang et al., 2014 ; Pereiro et al., 2020 ). Subsequently, the antiviral function of PTEN in SVCV-infected zebrafish models and HCV-infected Huh-7.5 cell model was confirmed through PTEN overexpression ( Wu et al., 2017 ; Pereiro et al., 2020 ). Therefore, the downregulation of PTEN in chicken infected with IBDV might be a mechanism of IBDV evasion from host immunity.…”

“…(2016) reported that PTEN plays a pivotal role in the induction of type I IFN by controlling the import of IRF3, a master transcription factor responsible for IFN-β production, into the nucleus. In zebrafish, PTEN is involved in the regulation of the expression of numerous immune genes and plays differential roles in immunity and response against viral infections ( Pereiro et al., 2020 ). In the present study, the PTEN mRNA level in the bursa was downregulated after chickens were infected with IBDV.…”

“…(2016) reported that PTEN functions in antiviral immunity by regulating the import of interferon regulatory factor 3 ( IRF3 ) into the nucleus and inducing type I interferon ( IFN ) production. Pereiro et al. (2020) demonstrated that PTEN responds against viral infections in zebrafish by regulating the expression of numerous immune genes.…”

Genomic Medicine and Advances in Vaccine Technology and Development in the Developing and Developed World

“…Another interesting aspect that is coming under increased scrutiny is the interaction between host and vaccine. Studies conducted on zebrafish by Pereiro et al, for instance, have proven that phosphatase and TENsin homolog on chromosome 10 (PTEN) can reduce viral spreading but increase viral replication during viral infections, which could impact the effect of vaccinations [ 33 ]. Even more interestingly, recent studies have gained insight into the role of γδT cells, which apparently interact in a virtuous circle with immunoglobulin G (IgG), as shown by de Sousa et al [ 34 ].…”