Our findings suggest a potentially novel therapeutic approach to seasonal, zoonotic avian, and pandemic influenza-the use of phosphoantigens to activate gammadelta T cells against influenza virus infections.

As shown in humanized mice, a population of Vγ9Vδ2 T cells can reduce the severity and mortality of disease caused by infection with human and avian influenza viruses.

While few children and young adults have cross-protective antibodies to the pandemic H1N1 2009 (pdmH1N1) virus, the illness remains mild. The biological reasons for these epidemiological observations are unclear. In this study, we demonstrate that the bulk memory cytotoxic T lymphocytes (CTLs) established by seasonal influenza viruses from healthy individuals who have not been exposed to pdmH1N1 can directly lyse pdmH1N1-infected target cells and produce gamma interferon (IFN-␥) and tumor necrosis factor alpha (TNF-␣). Using influenza A virus matrix protein 1 (M1 58-66 ) epitope-specific CTLs isolated from healthy HLA-A2 ؉ individuals, we further found that M1 58-66 epitope-specific CTLs efficiently killed both M1 58-66 peptide-pulsed and pdmH1N1-infected target cells ex vivo. These M1 58-66 -specific CTLs showed an effector memory phenotype and expressed CXCR3 and CCR5 chemokine receptors. Of 94 influenza A virus CD8 T-cell epitopes obtained from the Immune Epitope Database (IEDB), 17 epitopes are conserved in pdmH1N1, and more than half of these conserved epitopes are derived from M1 protein. In addition, 65% (11/17) of these epitopes were 100% conserved in seasonal influenza vaccine H1N1 strains during the last 20 years. Importantly, seasonal influenza vaccination could expand the functional M1 58-66 epitope-specific CTLs in 20% (4/20) of HLA-A2 ؉ individuals. Our results indicated that memory CTLs established by seasonal influenza A viruses or vaccines had cross-reactivity against pdmH1N1. These might explain, at least in part, the unexpected mild pdmH1N1 illness in the community and also might provide some valuable insights for the future design of broadly protective vaccines to prevent influenza, especially pandemic influenza.

Influenza is an acute respiratory viral disease that is transmitted in the first few days of infection. Evasion of host innate immune defenses, including natural killer (NK) cells, is important for the virus's success as a pathogen of humans and other animals. NK cells encounter influenza viruses within the microenvironment of infected cells and are important for host innate immunity during influenza virus infection. It is therefore important to investigate the direct effects of influenza virus on NK cells. In this study, we demonstrated for the first time that influenza virus directly infects and replicates in primary human NK cells. Viral entry into NK cells was mediated by both clathrin-and caveolin-dependent endocytosis rather than through macropinocytosis and was dependent on the sialic acids on cell surfaces. In addition, influenza virus infection induced a marked apoptosis of NK cells. Our findings suggest that influenza virus can directly target and kill NK cells, a potential novel strategy of influenza virus to evade the NK cell innate immune defense that is likely to facilitate viral transmission and may also contribute to virus pathogenesis.

BackgroundInfection with hepatitis B virus (HBV) in pregnant women may be a threat for both mothers and fetuses. This study was performed to explore the impact of maternal HBV carrier status on pregnancy outcomes.MethodsWe conducted a prospective cohort study at the Obstetrics & Gynecology Hospital of Nantong University between January 1, 2012 and September 30, 2015. A consecutive sample of 21,004 pregnant women, 513 asymptomatic HBV carriers and 20,491 non-HBV controls, was included in this study. The main outcomes of interest were selected pregnancy outcomes including miscarriage, stillbirth, preterm birth (PTB), gestational diabetes (GDM), intrahepatic cholestasis of pregnancy (ICP), preterm premature rupture of the membrane (PPROM), low birth weight (LBW), small for gestational age (SGA) and Apgar scores. The incidence of adverse pregnancy outcomes between asymptomatic HBV carriers and non-HBV controls were compared using the chi-square test and logistic regression. P values were two sided, and P <0.05 was considered to indicate statistical significance.ResultsThe incidences of stillbirth, PTB, GDM, ICP, PPROM, LBW, and SGA were similar between the HBV carrier and non-HBV groups. The proportion of miscarriage was significantly higher among the HBV carriers than the controls (9.36 % vs 5.70 %; P <0.001). After using multivariate modelling to adjust for possible socio-demographical variables and obstetric complications, women with HBV carrier status were still more likely to have miscarriage (adjusted OR 1.71, 95 % CI 1.23–2.38). In addition, the incidences of other maternal and neonatal outcomes were similar between the two groups.ConclusionMaternal HBV carrier status may be an independent risk factor for miscarriage and careful surveillance is warranted.

␥␦ T cells are essential constituents of antimicrobial and antitumor defenses. We have recently reported that phosphoantigen isopentenyl pyrophosphate (IPP)-expanded human V␥9V␦2 T cells participated in antiinfluenza virus immunity by efficiently killing both human and avian influenza virus-infected monocyte-derived macrophages (MDMs) in vitro. However, little is known about the noncytolytic responses and trafficking program of ␥␦ T cells to influenza virus. In this study, we found that V␥9V␦2 T cells expressed both type 1 cytokines and chemokine receptors during influenza virus infection, and IPP-expanded cells had a higher capacity to produce gamma interferon (IFN-␥). Besides their potent cytolytic activity against pandemic H1N1 virus-infected cells, IPP-activated ␥␦ T cells also had noncytolytic inhibitory effects on seasonal and pandemic H1N1 viruses via IFN-␥ but had no such effects on avian H5N1 or H9N2 virus. Avian H5N1 and H9N2 viruses induced significantly higher CCL3, CCL4, and CCL5 production in V␥9V␦2 T cells than human seasonal H1N1 virus. CCR5 mediated the migration of V␥9V␦2 T cells toward influenza virus-infected cells. Our findings suggest a novel therapeutic strategy of using phosphoantigens to boost the antiviral activities of human V␥9V␦2 T cells against influenza virus infection.

Abstract Background To control the spread of 2019 novel coronavirus disease (COVID-19), China sealed Wuhan on 23 January 2020 and soon expanded lockdown to 12 other cities in Hubei province. We aimed to describe the epidemiological characteristics in one of the cities and highlight the effect of current implemented lockdown and nonpharmaceutical interventions. Methods We retrieved data of reported cases in Huangshi and Wuhan from publicly available disease databases. Local epidemiological data on suspected or confirmed cases in Huangshi were collected through field investigation. Epidemic curves were constructed with data on reported and observed cases. Results The accumulated confirmed COVID-19 cases and fatality in Huangshi were reported to be 1015 and 3.74%, respectively, compared with 50006 and 5.08% in Wuhan until 27 March 2020. Right after 24 January, the epidemic curve based on observed cases in Huangshi became flattened. And 1 February 2020 was identified as the “turning point” as the epidemic in Huangshi faded soon afterward. COVID-19 epidemic was characterized by mild cases in Huangshi, accounting for 82.66% of total cases. Moreover, 50 asymptomatic infections were identified in adults and children. In addition, we found confirmed cases in 19 familial clusters and 21 healthcare workers, supporting interhuman transmission. Conclusions Our study reported the temporal dynamics and characteristics of the COVID-19 epidemic in Huangshi city, China, across the unprecedented intervention. Such new epidemiological inference might provide further guidance on current lockdown measures in high-risk cities and, subsequently, help improve public health intervention strategies against the pandemic on the country and global levels.

IMPORTANCE There is insufficient evidence on the efficacy of masks in the general population for the prevention of coronavirus disease 2019 (COVID-19) in public areas. Therefore, it is imperative to investigate the association of mandatory mask-wearing policies with behaviors associated with the transmission of COVID-19.OBJECTIVE To assess the association of mask wearing with face-touching behavior among the general population in public areas. DESIGN, SETTING, AND PARTICIPANTSThis cross-sectional study used videos recorded in public transportation stations, streets, and parks among the general population in China,