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KPNA2/importin-alpha1 (karyopherin subunit alpha 2) is the primary nucleocytoplasmic transporter for some transcription factors to activate cellular proliferation and differentiation. Aberrant increase of KPNA2 level is identified as a prognostic marker in a variety of cancers. Yet, the turnover mechanism of KPNA2 remains unknown. Here, we demonstrate that KPNA2 is degraded via the chaperone-mediated autophagy (CMA) and that Zika virus (ZIKV) enhances the KPNA2 degradation. KPNA2 contains a CMA motif, which possesses an indispensable residue Gln109 for the CMA-mediated degradation. RNAi-mediated knockdown of LAMP2A, a vital component of the CMA pathway, led to a higher level of KPNA2. Moreover, ZIKV reduced KPNA2 via the viral NS2A protein, which contains an essential residue Thr100 for inducing the CMA-mediated KPNA2 degradation. Notably, mutant ZIKV with T100A alteration in NS2A replicates much weaker than the wild-type virus. Also, knockdown of KPNA2 led to a higher ZIKV viral yield, which indicates that KPNA2 mediates certain antiviral effects. These data provide insights into the KPNA2 turnover and the ZIKV-cell interactions. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) is a fecal-oral-transmitted viral pathogen causing several large outbreaks of hepatitis across the world. HEV-mediated hepatitis has a mortality rate from 0.5 to 3% in young adults but is up to 30% in pregnant women. HEV is also a zoonotic pathogen as it has been isolated from different mammalian hosts including the pig, rabbit, rat, ferret, bat and deer. As an invading pathogen, HEV needs to overcome the host innate immune response to establish infection. Notable progress has been recently made in HEV mechanisms of antagonizing the host innate immune responses. In this review, we elaborate on the HEV interplay with host interferon induction while briefly summarizing the major aspects of HEV biology and host interferon induction to assist the understanding of the virus-host interaction. [ABSTRACT FROM AUTHOR]