Morphofunctional Characteristics of Pulmonary Surfactant System and Its Effect on Immune Cells in Influenza A (H1N1) Pathogenesis

There is an annual increase of influenza-related SARI cases in winter months. Despite the high relevance of this problem, influenza pathogenesis and the role of surfactant system and its SP-A (surfactant protein A) enzyme in antiviral defense remain poorly understood. SP-A activates macrophage M1 polarization and triggers an antiviral response due to the activation of T-cells and dendritic cells. Therefore, surfactant system is an important element of infection protection and a promising therapeutic target.

Epidemiology and Genotypic Diversity of Eurasian Avian-Like H1N1 Swine Influenza Viruses in China

Eurasian avian-like H1 N1(EA H1 N1)swine influenza virus(SIV)outside European countries was first detected in Hong Kong Special Administrative Region(Hong Kong,SAR)of China in 2001.Afterwards,EA H1 N1 SIVs have become predominant in pig population in this country.However,the epidemiology and genotypic diversity of EA H1 N1 SIVs in China are still unknown.Here,we collected the EA H1 N1 SIVs sequences from China between 2001 and 2018 and analyzed the epidemic and phylogenic features,and key molecular markers of these EA H1 N1 SIVs.Our results showed that EA H1 N1 SIVs distributed in nineteen provinces/municipalities of China.After a long-time evolution and transmission,EA H1 N1 SIVs were continuously reassorted with other co-circulated influenza viruses,including 2009 pandemic H1 N1(A(H1 N1)pdm09),and triple reassortment H1 N2(TR H1 N2)influenza viruses,generated 11 genotypes.Genotype 3 and 5,both of which were the reassortments among EA H1 N1,A(H1 N1)pdm09 and TR H1 N2 viruses with different origins of M genes,have become predominant in pig population.Furthermore,key molecular signatures were identified in EA H1 N1 SIVs.Our study has drawn a genotypic diversity image of EA H1 N1 viruses,and could help to evaluate the potential risk of EA H1 N1 for pandemic preparedness and response.

Reduning plus ribavirin display synergistic activity against severe pneumonia induced by H1N1 influenza A virus in mice

OBJECTIVE:To investigate synergistic effect of Reduning(RDN)injection plus ribavirin against severe pneumonia induced by H1 N1 influenza A virus in mice.METHODS:We established a mouse model of severe pneumonia induced by influenza A virus by infecting Balb/c mice with CA07 virus.We randomly assigned the infected mice into four groups,and treated them with normal saline(NS group),RDN(injection,86.6 mg/kg),ribavirin(injection,66.6 mg/kg)or double Ribavirin plus RDN group,the same dosage as used in the single treatments)for 5 d.Lung index and lung pathology were recorded or calculated in terms of the curative effective.Cytokines,NOD-like receptor family pyrin domain containing 3(NLRP3)inflammasome related protein including caspase-associated recruitment domain(CARD)domain Apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),caspase-1 and NOD-like receptor family,pyrin domain containing 3(NLRP3),and reactive oxygen species were simultaneously investigated.RESULTS:RDN plus ribavirin treatment,not RDN or ribavirin alone,provided a significant survival benefit to the influenza A virus-infected mice.The combination treatment protected the mice against severe influenza infection by attenuating the severe lung injury.The combined treatment also reduced the viral titers in mouse lungs and lung index,downregulated their immunocytokine levels,including IL-1βand IL-18,and down regulated the NLRP3,especially the transcription and translation of caspase-1.Meanwhile NS group had significantly higher reactive oxygen species(ROS)expression which could was dramatically reduced by the treatment of RDN plus ribavirin.CONCLUSION:Our study showed that RDN combined with ribavirin could protect the mice,and reduce the lung immunopathologic damage caused by severe influenza pneumonia.The mechanism could be that it reduced ROS produce and inhibited NLRP3 inflammasome activation so that mainly lower the downstream inflammatory cytokines IL-1βand IL-18.

Mutations associated with egg adaptation of influenza A(H1N1)pdm09 virus in laboratory based surveillance in China, 2009–2016

Mutations of influenza virus associated with adaptation occurring during passage in embryonated chicken eggs could result in antigenic change or reduced vaccine effectiveness.In this study,we investigated the mutations of influenza A(H1N1)pdm09 egg isolates from the Chinese National Influenza Surveillance Network between 2009 and 2016.Thirteen mutations were identified in the hemagglutinin(HA)protein from viruses passaged in eggs,in comparing to those in cells.After scanning public database,four mutations,D127E,L191I,D222G/N and Q223R in HA1,which may alter the receptor-binding specificity,were observed frequently.Although the A(H1N1)pdm09 virus has evolved in human for nearly ten years,most egg-cultured viruses acquired one or more further mutations.Using the egg isolates for influenza surveillance requires extra caution because of these selected mutations,and their impacts on antigenicity and receptor-binding property need further evaluation.Currently,most of the influenza vaccines are produced using egg isolates,particularly in China.Thus,there is an urge to promote the establishment of an alternative influenza vaccine production platform.

Detection and pathogenesis of a novel swine H3N2 influenza virus containing three genes from the 2009 pandemic H1N1 influenza viruses in Korea in 2015

Dear Editor,Influenza A viruses cause pandemics at an interval of approximately 10–40 years,and pigs are regarded as a'mixing vessel'because they are easily infected with avian and human influenza viruses(Ito et al.,1998).According to previous studies,H3N2,H1N2,and

Rapid detection of influenza A(H1N1)virus by conductive polymer-based nanoparticle via optical response to virus-specific binding

A recurrent pandemic with unpredictable viral nature has implied the need for a rapid diagnostic technology to facilitate timely and appropriate countermeasures against viral infections.In this study,conductive polymer-based nanoparticles have been developed as a tool for rapid diagnosis of influenza A(H1N1)virus.The distinctive property of a conductive polymer that transduces stimulus to respond,enabled immediate optical signal processing for the specific recognition of H1N1 virus.Conductive poly(aniline-co-pyrrole)-encapsulated polymeric vesicles,functionalized with peptides,were fabricated for the specific recognition of H1N1 virus.The low solubility of conductive polymers was successfully improved by employing vesicles consisting of amphiphilic copolymers,facilitating the viral titer-dependent production of the optical response.The optical response of the detection system to the binding event with H1N1,a mechanical stimulation,was extensively analyzed and provided concordant information on viral titers of H1N1 virus in 15 min.The specificity toward the H1N1 virus was experimentally demonstrated via a negative optical response against the control group,H3N2.Therefore,the designed system that transduces the optical response to the target-specific binding can be a rapid tool for the diagnosis of H1N1.

Antigenic Drift of the Hemagglutinin from an Influenza A(H1N1) pdm09 Clinical Isolate Increases its Pathogenicity In Vitro

The influenza A(H1 N1)pdm09 virus emerged in 2009 and has been continuously circulating in humans for over ten years.Here,we analyzed a clinical influenza A(H1 N1)pdm09-infected patient case hospitalized for two months in Guangdong(from December 14,2019 to February 15,2020).This isolate,named A/Guangdong/LCF/2019(LCF/19),was genetically sequenced,rescued by reverse genetics,and phylogenetically analyzed in the context of other relevant pdm09 isolates.Compared with earlier isolates,this pdm09 virus’s genetic sequence contains four substitutions,S186 P,T188 I,D190 A,and Q192 E,of the hemagglutinin(HA)segment at position 186–192(H3 numbering)in the epitope Sb,and two of which are located at the 190-helix.Phylogenetic analysis indicated that the epitope Sb started undergoing a rapid antigenic change in2018.To characterize the pathogenicity of this novel substitution motif,a panel of reassortant viruses containing the LCF/2019 HA segment or the chimeric HA segment with the four substitutions were rescued.Kinetic growth data revealed that the reassortant viruses,including the LCF/2019 with the PTIAAQE substitution,propagated faster than those rescued ones having the STTADQQ motif in the epitope Sb in Madin-Darby Canine Kidney(MDCK)cells.The HI test showed that the binding activity of escape mutant to 2018 pdm09 sera was weaker than GLW/2018,suggesting that old vaccines might not effectively protect people from infection.Due to the difference in the selection of vaccine strains,people vaccinated in the southern hemisphere could still suffer a severe infection if infected with this antigenic drift pdm09 virus.