US28, a Virally-Encoded GPCR as an Antiviral Target for Human Cytomegalovirus Infection

Viruses continue to evolve a new strategy to take advantage of every aspect of host cells in order to maximize their survival. Due to their central roles in transducing a variety of transmembrane signals, GPCRs seem to be a prime target for viruses to pirate for their own use. Incorporation of GPCR functionality into the genome of herpesviruses has been demonstrated to be essential for pathogenesis of many herpesviruses-induced diseases. Here, we introduce US28 of human cytomegalovirus (HCMV) as the best-studied example of virally-encoded GPCRs to manipulate host GPCR signaling. In this review, we wish to summarize a number of US28-related topics including its regulation of host signaling pathways, its constitutive internalization, its structural and functional analysis, its roles in HCMV biology and pathogenesis, its proliferative activities and role in oncogenesis, and pharmacological modulation of its biological activities. This review will aid in our understanding of how pathogenic viruses usurp the host GPCR signaling for successful viral infection. This kind of knowledge will enable us to build a better strategy to control viral infection by normalizing the virally-dysregulated host GPCR signaling.

The influence of intracellular keratin 8 on hepatitis C virus replication / 药学学报

The level of intracellular keratin 8(KRT-8) is associated with liver diseases, whose expression is increased in hepatitis C virus (HCV)-infected patients with hepatocarcinoma and in cultural cells infected with HCV. However, it is not clear whether KRT-8 will impact HCV replication. In this paper, the HCV replication was analyzed in response to high expression and silence of KRT-8. The inhibitory activities against wild-type and mutant HCV were also analyzed by silence of KRT-8 or combined with known anti-HCV drug telaprevir. Results showed that the protein level of KRT-8 was increased in proportion with the HCV replication. The high expression was found to facilitate HCV replication, while the silence of KRT-8 was able to inhibit HCV replication and enhanced the anti-HCV activity of telaprevir. It also inhibited A156T and D168V mutant HCV, which are resistant to protease inhibitors. These results suggest that KRT-8 is a co-factor for HCV replication. Down-regulation of KRT-8 can inhibit wild type and mutant HCV replication to enhance the anti-HCV activity of known anti-HCV drugs. Therefore, KRT-8 may be a new target in the development of anti-HCV agents.

Ebola virus and advances in studies on drugs used against it / 中草药

Ebola virus (EBOV) is a highly lethal virus leading to rapidly fatal hemorrhagic fever in humans and other vertebrates, whose mortality rate could be 90%. Up to now, there is still no effective anti-virus drug or vaccine. Because of severe public health hazard, EBOV has been listed in the most dangerous viruses to humans by WHO. Due to the outbreak of Ebola hemorrhagic fever (EHF) in Africa in 2014, the correlation research on EBOV has become the hot topic in virology. The general characteristics, structure composition, life cycle of virus, pathogenesis generalization, clinical manifestation of EHF were described in this review. The recent advances about the antiviral targets and drugs were also summarized, as well as prospect on the application of Chinese materia medica in anti-EBOV. In a word, the understanding of EBOV and drug development could be promoted by this review.