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.
Highlights
PTEN is a tumor suppression gene that is mutated in a wide variety of tumors [1]
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
Summary
PTEN (phosphatase and TENsin homolog on chromosome 10) is a tumor suppression gene that is mutated in a wide variety of tumors [1]. This protein acts as a bifunctional phosphatase of lipids and proteins [2]. As a negative regulator of the phosphatidylinositol 3–kinase (PI3K)/AKT pathway due to its PI (phosphoinositide) 3-phosphatase activity, PTEN is involved in several cellular mechanisms, including proliferation, cell migration, apoptosis, cell survival, and metabolism [1]. The recognized activities of PTEN have been expanded to include other phosphatase-independent activities and even PI3K/AKT pathway-independent activities [3]. Some publications have reported the involvement of mammalian PTEN in different immunological processes, including the activity, proliferation, survival, and differentiation of lymphocytes [7,8,9,10]
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