Zika virus (ZIKV) is primarily transmitted by Aedes mosquitoes in the subgenus Stegomyia but can also be transmitted sexually and vertically in humans. STAT1 is an important downstream factor that mediates type I and II interferon signaling. In the current study, we showed that mice with STAT1 knockout (Stat1-/-) were highly susceptible to ZIKV infection. As low as 5 plaque-forming units of ZIKV could cause viremia and death in Stat1-/- mice. ZIKV replication was initially detected in the spleen but subsequently spread to the brain with concomitant reduction of the virus in the spleen in the infected mice. Furthermore, ZIKV could be transmitted from mosquitoes to Stat1-/- mice back to mosquitoes and then to naïve Stat1-/- mice. The 50% mosquito infectious dose of viremic Stat1-/- mouse blood was close to 810 focus-forming units (ffu)/ml. Our further studies indicated that the activation of macrophages and conventional dendritic cells were likely critical for the resolution of ZIKV infection. The newly developed mouse and mosquito transmission models for ZIKV infection will be useful for the evaluation of antiviral drugs targeting the virus, vector, and host.

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Hepatitis B virus (HBV) is a hepatotropic virus and an important human pathogen. There are an estimated 296 million people in the world that are chronically infected by this virus, and many of them will develop severe liver diseases including hepatitis, cirrhosis and hepatocellular carcinoma (HCC). HBV is a small DNA virus that replicates via the reverse transcription pathway. In this review, we summarize the molecular pathways that govern the replication of HBV and its interactions with host cells. We also discuss viral and non-viral factors that are associated with HBV-induced carcinogenesis and pathogenesis, as well as the role of host immune responses in HBV persistence and liver pathogenesis.

Hepatitis B virus (HBV) DNA replication takes place inside the viral core particle and is dependent on autophagy. Here we show that HBV core particles are associated with autophagosomes and phagophores in cells that productively replicate HBV. These autophagic membrane-associated core particles contain almost entirely the hypophosphorylated core protein and are DNA replication competent. As the hyperphosphorylated core protein can be localized to phagophores and the dephosphorylation of the core protein is associated with the packaging of viral pregenomic RNA (pgRNA), these results are in support of the model that phagophores can serve as the sites for the packaging of pgRNA. In contrast, in cells that replicate HBV, the precore protein derivatives, which are related to the core protein, are associated with autophagosomes but not with phagophores via a pathway that is independent of its signal peptide. Interestingly, when the core protein is expressed by itself, it is associated with phagophores but not with autophagosomes. These observations indicate that autophagic membranes are differentially involved in the trafficking of precore and core proteins. HBV induces the fusion of autophagosomes and multivesicular bodies and the silencing of Rab11, a regulator of this fusion, is associated with the reduction of release of mature HBV particles. Our studies thus indicate that autophagic membranes participate in the assembly of HBV nucleocapsids, the trafficking of HBV precore and core proteins, and likely also the egress of HBV particles.

After aerosolization of a bovine strain of parainfluenza type 3 virus, the pathogenesis of the virus was followed from the trachea to the bronchioalveolar compartments of the lung of colostrum-free calves and of conventionally reared calves during a 5to 12-day postexposure interval. By tissue titration, plaque assay, and electron microscopy, it was found that virus infection could be established in colostrum-free calves as well as in conventionally reared calves, even though sequential changes of virus replication were observed mainly in the infected colostrum-free calves during the 5to 6-day postexposure periods. Electron microscopy demonstrations of (i) aggregates of viral nucleocapsids in the cytoplasm, (ii) alterations of cilia and basal bodies, (iii) dissolution of cytoplasmic membranes, and (iv) the shedding of virus into luminal spaces confirmed that epithelial cells of the respiratory tract were the primary target cells for the virus replication leading to cell destruction. These observations revealed further that productive infection was more efficient in the bronchioalveolar regions than in the tracheal regions, although large aggregates of viral nucleocapsids and destructive changes were more pronounced in the tracheal epithelium. The finding that parainfluenza type 3 virus replicates in the alveolar type II cells suggests that changes in surfactant production may occur during the peak of infection of these cells. The demonstration of virus budding through the basement membrane of small bronchioles and the presence of virus particles in the interstitial regions imply that one of the host defense lines, the basement membrane, may be impaired by virus invasion.