The miRNAs of Herpes Simplex Virus(HSV)

Herpes simplex virus (HSV) is a group of common human pathogens with two serotypes HSV-1 and HSV-2.The prevalence of HSV is worldwide.It primarily infects humans through epithelial cells,when it introduces a latent infection into the nervous system.During viral latency,only a region known as the latency-associated transcript (LAT) is expressed.The discovery of HSV miRNAs helps to draw a larger picture of the infection and pathogenesis of the virus.This review summarizes miRNAs found in HSV-1 and HSV-2 so far.The functional studies of miRNAs in HSV to date indicate that they play a stage-specific role coordinated with viral proteins to maintain the virus life cycle.

Pulmonary immune cells and inflammatory cytokine dysregulation are associated with mortality of IL-1R1^(-/-) mice infected with influenza virus(H1N1)

Respirovirus infection can cause viral pneumonia and acute lung injury （ALl）. The interleukin-1 （IL-1） family consists of proinflammatory cytokines that play essential roles in regulating immune and inflammatory responses in vivo. IL-1 signaling is associated with protection against respiratory influenza virus infection by mediation of the pulmonary anti-viral immune response and inflammation. We analyzed the infiltration lung immune leukocytes and cytokines that contribute to inflammatory lung pathology and mortality of fatal H1N1 virus-infected IL-1 receptor 1 （IL-1R1） deficient mice. Results showed that early innate immune cells and cytokine/chemokine dysregulation were observed with significantly decreased neutrophil infiltration and IL-6, TNF-α, G-CSF, KC, and MIP-2 cytokine levels in the bronchoalveolar lavage fluid of infected IL-1R1^-/- mice in comparison with that of wild type infected mice. The adaptive immune response against the H1N1 virus in IL-1 R1^-/- mice was impaired with downregulated anti-viral Thl cell, CD8＋ cell, and antibody functions, which contributes to attenuated viral clearance. Histological analysis revealed reduced lung inflammation during early infection but severe lung pathology in late infection in IL-1R1^-/- mice compared with that in WT infected mice. Moreover, the infected IL-1R1^--/ mice showed markedly reduced neutrophil generation in bone marrow and neutrophil recruitment to the inflamed lung. Together, these results suggest that IL-1 signaling is associated with pulmonary anti-influenza immune response and inflammatory lung injury, particularly via the influence on neutrophil mobilization and inflammatory cytokine/chemokine production.

HSV-1 stimulation-related protein HSRG1 inhibits viral gene transcriptional elongation by interacting with Cyclin T2

The protein encoded by HSRG1(HSV-1 stimulation-related gene 1) is a virally induced protein expressed in HSV-1-infected cells.We have already reported that HSRG1 is capable of interacting with transcriptional regulator proteins.To further analyze the effects of HSRG1 on the regulation of viral gene transcription,we expressed the HSRG1 protein in transfected cells and found that it postpones the proliferation of HSV-1.CAT(chloramphenicol acetyltransferase) assays also revealed that HSRG1 reduces transcription from HSV-1 promoters.Yeast two-hybrid and immunoprecipitation assays indicated that HSRG1 interacts with Cyclin T2,the regulatory subunit of P-TEFb,which is required for transcription elongation by RNA Pol II(RNAP II) ,and that amino acid residues 1-420 in Cyclin T2 are important for binding with HSRG1.Fluorescence assays suggested that the cellular localizations of those two proteins are influenced by their interaction.Further analyses with CAT assays revealed that HSRG1 inhibits the transcriptional activation by Cyclin T2 of viral promoters.Our results suggested that the inhibitory effects of HSRG1 on viral replication and proliferation are probably induced by its binding to Cyclin T2.Therefore,it is likely that HSRG1 inhibits viral gene transcriptional elongation by interacting with Cyclin T2.

MCMV-based vaccine vectors expressing full-length viral proteins provide long-term humoral immune protection upon a single-shot vaccination

Global pandemics caused by influenza or coronaviruses cause severe disruptions to public health and lead to high morbidity and mortality.There remains a medical need for vaccines against these pathogens.CMV(cytomegalovirus)is aβ-herpesvirus that induces uniquely robust immune responses in which remarkably large populations of antigen-specific CD8+T cells are maintained for a lifetime.Hence,CMV has been proposed and investigated as a novel vaccine vector for expressing antigenic peptides or proteins to elicit protective cellular immune responses against numerous pathogens.We generated two recombinant murine CMV(MCMV)vaccine vectors expressing hemagglutinin(HA)of influenza A virus(MCMV^(HA))or the spike protein of severe acute respiratory syndrome coronavirus 2(MCMV^(S)).A single injection of MCMVs expressing either viral protein induced potent neutralizing antibody responses,which strengthened over time.Importantly,MCMV^(HA)-vaccinated mice were protected from illness following challenge with the influenza virus,and we excluded that this protection was due to the effects of memory T cells.Conclusively,we show here that MCMV vectors induce not only long-term cellular immunity but also humoral responses that provide long-term immune protection against clinically relevant respiratory pathogens.

The 2009 pandemic A/Wenshan/01/2009 H1N1 induces apoptotic cell death in human airway epithelial cells

In 2009,a novel swine-origin H1N1 influenza virus emerged in Mexico and quickly spread to other countries,including China.This 2009 pandemic H1N1 can cause human respiratory disease,but its pathogenesis remains poorly understood.Here,we studied the infection and pathogenesis of a new 2009 pandemic strain,A/Wenshan/01/2009 H1N1,in China in human airway epithelial cell lines compared with contemporary seasonal H1N1 influenza virus.Our results showed that viral infection by the A/Wenshan H1N1 induced significant apoptotic cell death in both the human nasopharyngeal carcinoma cell line CNE-2Z and the human lung adenocarcinoma cell line A549.The A/Wenshan H1N1 virus enters both of these cell types more efficiently than the seasonal influenza virus.Viral entry in both cell lines was shown to be mediated by clathrin-and dynamin-dependent endocytosis.Therefore,we discovered that the 2009 pandemic H1N1 strain,A/Wenshan/01/2009,can induce apoptotic cell death in epithelial cells of the human respiratory tract,suggesting a molecular pathogenesis for the 2009 pandemic H1N1.