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Porcine reproductive and respiratory syndrome virus (PRRSV) infection inhibits swine leukocyte antigen class I (SLA-I) expression in pigs, resulting in inefficient antigen presentation and subsequent low levels of cellular PRRSV-specific immunity as well as persistent viremia. We previously observed that the non-structural protein 4 (nsp4) of PRRSV contributed to inhibition of the β2-microglobulin (β2M) and SLA-I expression in cells. Here, we constructed a series of nsp4 mutants with different combination of amino acid mutations to attenuate the inhibitory effect of nsp4 on β2M and SLA-I expression. Almost all nsp4 mutants exogenously expressed in cells showed an attenuated effect on inhibition of β2M and SLA-I expression, but the recombinant PRRSV harboring these nsp4 mutants failed to be rescued with exception of the rPRRSV-nsp4-mut10 harboring three amino acid mutations. However, infection of rPRRSV-nsp4-mut10 not only enhanced β2M and SLA-I expression in both cells and pigs but also promoted the DCs to active the CD3+CD8+T lymphocytes more efficiently, as compared with its parental PRRSV (rPRRVS-nsp4-wt). These data suggested that the inhibition of nsp4-mediated β2M downregulation improved β2M/SLA-I expression in pigs. • The Nsp4 gene of PRRSV on virus level inhibit the expression of β2M/SLA-I gene in pigs in this research filed. • The three amino acid sites of Nsp4 gene we have screened play a key role in inhibition of the expression of β2M/SLA-I gene in pigs. • The rPRRSV-nsp4-mut10 can induce more expression of β2M/SLA-I which accelerates the clearance of PRRSV in pigs. [ABSTRACT FROM AUTHOR]

Highlights: [•] miR-30a represses Eya2 expression by binding to the 3′-untranslated region of Eya2. [•] The miR-30a/EYA2 axis regulates breast cancer cell proliferation and migration. [•] The miR-30a/EYA2 axis modulates G1/S cell cycle progression. [•] The miR-30a/EYA2 axis is dysregulated in breast cancer patients. [ABSTRACT FROM AUTHOR]

Abstract: HCV and HBV are the major causes of chronic liver diseases worldwide. Patients with both viruse’s co-infection tend to develop severer liver diseases and are at high risk of liver-related death. NS5A protein of HCV plays key roles in HCV replication and inhibition of host immune responses. In this study, we described the establishment of HepG2-derived cell line that stably expresses NS5A protein and the application of a cellular system for HBV replication based on a recombinant adenovirus carrying HBV genome. Our results demonstrated that NS5A enhances the expression of S and E proteins of HBV, as well as the synthesis of viral DNA. Moreover, we showed that NS5A assists HBV to escape interferon responses. These data suggested that NS5A of HCV may employ multiple strategies contributing to the enhancement of HBV replication and interferon resistance during the co-infection of HCV and HBV. [Copyright &y& Elsevier]

Abstract: The overexpression of osteopontin is associated with various inflammatory liver diseases. Interestingly, each of these diseases is also associated with IL-17 expression. Therefore, we sought to determine whether there is any mechanistic link between osteopontin and IL-17. Herein we show that IL-17 and osteopontin levels were significantly increased in patients with chronic hepatitis B. We found that IL-17 and osteopontin levels increased similarly in mice with concanavalin A-induced hepatitis. Both osteopontin- and IL-17-deficient mice were resistant to concanavalin A-induced hepatic injury. In addition, osteopontin markedly induced IL-17 expression by leukocytes (from humans and mice). This effect could be blocked by a specific antibody against osteopontin. β3 integrin (one of the osteopontin receptors) was critically involved in the induction of IL-17 production by osteopontin. Osteopontin-induced IL-17 expression was mediated through the p38, JNK, and NF-κB pathways. These findings suggest that osteopontin regulates IL-17 production during the pathogenesis of hepatitis and provide new evidence for the critical roles of osteopontin and IL-17 in hepatitis. [Copyright &y& Elsevier]