Rapid Semiautomated Subtyping of Influenza Virus Species during the 2009 Swine Origin Influenza A H1N1 Virus Epidemic in Milwaukee, Wisconsin

In 2009, a novel pandemic swine-origin influenza A (H1N1) virus caused a public emergency of international concern. Vaccination is the primary strategy for the control of influenza epidemics. However, the poor immunopotency of many vaccine antigens is a major barrier to the development of effective vaccines against influenza. Flagellin, a Toll-like receptor 5 (TLR5) ligand, has been used as an adjuvant to enhance the immunopotency of vaccines in preclinical studies. Here, we developed a recombinant candidate vaccine, HA1-2-fljB, in which the globular head of the hemagglutinin (HA) antigen (residues 62-284) from H1N1 virus was fused genetically to the N-terminus of <i>Salmonella typhimurium</i> ﬂjB. The recombinant HA1-2-fljB protein was expressed efficiently in<i> Escherichia coli</i>, and the immunogenicity and protective efficacy of recombinant HA1-2-fljB were evaluated in a mouse model. Immunization with HA1-2-fljB elicited robust IgG antibodies and neutralizing antibodies and completely protected the mice against infection by swine-origin influenza A/swine/Jangsu/38/2010 (H1N1). These results suggest that HA antigen placed at the N-terminus of flagellin is also an excellent starting point for creating a fusion HA1-2-fljB protein as a candidate vaccine, and the recombinant HA1-2-fljB protein will contribute to the development of a more effective vaccine against swine-origin influenza virus infection.

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Contemporary Seasonal Influenza A (H1N1) Virus Infection Primes for a More Robust Response To Split Inactivated Pandemic Influenza A (H1N1) Virus Vaccination in Ferrets

Clinical and Vaccine Immunology ◽

10.1128/cvi.00247-10 ◽

2010 ◽

Vol 17 (12) ◽

pp. 1998-2006 ◽

Cited By ~ 11

Author(s):

Ali H. Ellebedy ◽

Thomas P. Fabrizio ◽

Ghazi Kayali ◽

Thomas H. Oguin ◽

Scott A. Brown ◽

...

Keyword(s):

Influenza Virus ◽

Pandemic Influenza ◽

Influenza A ◽

Seasonal Influenza ◽

H1n1 Virus ◽

H1n1 Influenza ◽

Influenza Viruses ◽

Inactivated Vaccine ◽

H1n1 Influenza Virus ◽

Influenza A H1n1

ABSTRACT Human influenza pandemics occur when influenza viruses to which the population has little or no immunity emerge and acquire the ability to achieve human-to-human transmission. In April 2009, cases of a novel H1N1 influenza virus in children in the southwestern United States were reported. It was retrospectively shown that these cases represented the spread of this virus from an ongoing outbreak in Mexico. The emergence of the pandemic led to a number of national vaccination programs. Surprisingly, early human clinical trial data have shown that a single dose of nonadjuvanted pandemic influenza A (H1N1) 2009 monovalent inactivated vaccine (pMIV) has led to a seroprotective response in a majority of individuals, despite earlier studies showing a lack of cross-reactivity between seasonal and pandemic H1N1 viruses. Here we show that previous exposure to a contemporary seasonal H1N1 influenza virus and to a lesser degree a seasonal influenza virus trivalent inactivated vaccine is able to prime for a higher antibody response after a subsequent dose of pMIV in ferrets. The more protective response was partially dependent on the presence of CD8+ cells. Two doses of pMIV were also able to induce a detectable antibody response that provided protection from subsequent challenge. These data show that previous infection with seasonal H1N1 influenza viruses likely explains the requirement for only a single dose of pMIV in adults and that vaccination campaigns with the current pandemic influenza vaccines should reduce viral burden and disease severity in humans.

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The Modified JiuWei QiangHuo Decoction Alleviated Severe Lung Injury Induced by H1N1 Influenza Virus by Regulating the NF-κB Pathway in Mice

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2015/790739 ◽

2015 ◽

Vol 2015 ◽

pp. 1-12 ◽

Cited By ~ 1

Author(s):

Lijuan Chen ◽

Xin Yan ◽

Qianlin Yan ◽

Jiajun Fan ◽

Hai Huang ◽

...

Keyword(s):

Influenza Virus ◽

Lung Injury ◽

Influenza A ◽

H1n1 Virus ◽

Alternative Therapy ◽

Severe Pneumonia ◽

H1n1 Influenza ◽

Influenza A H1n1 ◽

Lung Injuries ◽

Severe Lung

A new approach to treat infections of highly pathogenic influenza virus is to inhibit excessive innate immune response. JiuWei QiangHuo decoction has been used for centuries for the treatment of pulmonary disorders in China. In this study, we evaluated the anti-inflammatory activities of the modified JiuWei QiangHuo (MJWQH) decoction in the treatment of influenza A (H1N1) virus-induced severe pneumonia in mice. The results showed that MJWQH significantly increased the survival rate of H1N1-infected mice and suppressed the production of TNF-α, IL-1, IL-6, MCP-1, RANTES, and IFN-αon day 4 after infection. Moreover, oral administration of MJWQH efficiently inhibited virus replication and alleviated the severity of lung injuries. The results also showed that MJWQH may have potential therapeutic effect on severe lung injury induced by H1N1 virus by regulating the NF-κB pathway. Our study suggested that MJWQH might be an alternative therapy for the treatment of viral pneumonia.

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Synergistic Antiviral Activity of S-033188/S-033447, a Novel Inhibitor of Influenza Virus Cap-Dependent Endonuclease, in Combination with Neuraminidase Inhibitors In Vitro

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx163.910 ◽

2017 ◽

Vol 4 (suppl_1) ◽

pp. S371-S371 ◽

Cited By ~ 4

Author(s):

Mitsutaka Kitano ◽

Atsuko Yamamoto ◽

Takeshi Noshi ◽

Makoto Kawai ◽

Ryu Yoshida ◽

...

Keyword(s):

Influenza Virus ◽

Influenza A ◽

Cultured Cells ◽

H1n1 Virus ◽

Mdck Cells ◽

Active Form ◽

Neuraminidase Inhibitors ◽

Dependent Endonuclease ◽

Influenza A H1n1

Abstract Background S-033447, an active form of orally available prodrug S-033188, is a novel small molecule inhibitor of cap-dependent endonuclease that is essential for influenza virus transcription and replication. In this study, we evaluated the inhibitory effect of S-033188 in combination with neuraminidase inhibitors on the replication of influenza A/H1N1 virus in cultured cells. Methods The inhibitory effects of S-033447 in combination with NA inhibitors on the cytopathic effect of A/PR/8/34 strain in Madin–Darby canine kidney cells cultured for 2 days were tested and EC50 were determined. The combination index (CI), which were obtained when S-033188 and NA inhibitor were added at the closest ratio of each EC50 value, were used for the evaluation of these combinational effects (Table 1). CI values were calculated by the Chou and Talalay method, in which combinational effect were determined according to the criteria as follows: synergistic if CI ≤ 0.8, additive if 0.8 < CI < 1.2, and antagonistic if CI ≥ 1.2. CI = (DA/A + B)/DA + (DB/A + B)/DB + (DA/A + B × DB/A + B)/(DA × DB) DA: the EC50 of S-033447 DB: the EC50 of NA inhibitor DA/A + B: the concentration of S-033447 giving 50% inhibition in combination with NA inhibitor at the closest ratio of each EC50 value DB/A + B: the concentration of NA inhibitor giving 50% inhibition in combination with S-033447 at the closest ratio of each EC50 value Results All CI values were lower than 0.8, under the condition that both S-033447 and NA inhibitor (oseltamivir acid, zanamivir hydrate, laninamivir, or peramivir trihydrate) were added at the closest ratio of each EC50 value (Table 1). Conclusion S-033447 in combination with oseltamivir acid, zanamivir hydrate, laninamivir, or peramivir trihydrate synergistically inhibited the replication of influenza A/H1N1 virus in MDCK cells. Disclosures All authors: No reported disclosures.

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Diagnostic Assay Recommended by the World Health Organization for Swine Origin Influenza A (H1N1) Virus Cross-Reacts with H5N1 Influenza Virus

Journal of Clinical Microbiology ◽

10.1128/jcm.01509-09 ◽

2009 ◽

Vol 47 (11) ◽

pp. 3789-3790 ◽

Cited By ~ 6

Author(s):

M. Peacey ◽

R. J. Hall ◽

J. Bocacao ◽

Q. S. Huang

Keyword(s):

Influenza Virus ◽

Influenza A ◽

H1n1 Virus ◽

World Health ◽

Diagnostic Assay ◽

H5n1 Influenza Virus ◽

H5n1 Influenza ◽

Influenza A H1n1 ◽

The World ◽

Health Organization

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Pathogenesis of Pandemic Influenza A (H1N1) and Triple-Reassortant Swine Influenza A (H1) Viruses in Mice

Journal of Virology ◽

10.1128/jvi.02742-09 ◽

2010 ◽

Vol 84 (9) ◽

pp. 4194-4203 ◽

Cited By ~ 95

Author(s):

Jessica A. Belser ◽

Debra A. Wadford ◽

Claudia Pappas ◽

Kortney M. Gustin ◽

Taronna R. Maines ◽

...

Keyword(s):

Influenza Virus ◽

Influenza A ◽

H1n1 Virus ◽

Swine Influenza Virus ◽

Swine Influenza ◽

The United States ◽

Chemokine Production ◽

Highly Pathogenic ◽

Influenza A H1n1 ◽

2009 H1n1

ABSTRACT The pandemic H1N1 virus of 2009 (2009 H1N1) continues to cause illness worldwide, primarily in younger age groups. To better understand the pathogenesis of these viruses in mammals, we used a mouse model to evaluate the relative virulence of selected 2009 H1N1 viruses and compared them to a representative human triple-reassortant swine influenza virus that has circulated in pigs in the United States for over a decade preceding the current pandemic. Additional comparisons were made with the reconstructed 1918 virus, a 1976 H1N1 swine influenza virus, and a highly pathogenic H5N1 virus. Mice were inoculated intranasally with each virus and monitored for morbidity, mortality, viral replication, hemostatic parameters, cytokine production, and lung histology. All 2009 H1N1 viruses replicated efficiently in the lungs of mice and possessed a high degree of infectivity but did not cause lethal disease or exhibit extrapulmonary virus spread. Transient weight loss, lymphopenia, and proinflammatory cytokine and chemokine production were present following 2009 H1N1 virus infection, but these levels were generally muted compared with a triple-reassortant swine virus and the 1918 virus. 2009 H1N1 viruses isolated from fatal cases did not demonstrate enhanced virulence in this model compared with isolates from mild human cases. Histologically, infection with the 2009 viruses resulted in lesions in the lung varying from mild to moderate bronchiolitis with occasional necrosis of bronchiolar epithelium and mild to moderate peribronchiolar alveolitis. Taken together, these studies demonstrate that the 2009 H1N1 viruses exhibited mild to moderate virulence in mice compared with highly pathogenic viruses.

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Seasonal H1N1 2007 influenza virus infection is associated with elevated pre‐exposure antibody titers to the 2009 pandemic influenza A (H1N1) virus

Clinical Microbiology and Infection ◽

10.1111/j.1469-0691.2010.03352.x ◽

2011 ◽

Vol 17 (5) ◽

pp. 732-737 ◽

Cited By ~ 13

Author(s):

M. Lemaitre ◽

M. Leruez‐Ville ◽

X.N. De Lamballerie ◽

N. Salez ◽

P. Garrone ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Pandemic Influenza ◽

Influenza A ◽

H1n1 Virus ◽

Influenza Virus Infection ◽

Influenza A H1n1 ◽

Antibody Titers

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Different Virucidal Activities of Hyperbranched Quaternary Ammonium Coatings on Poliovirus and Influenza Virus

Applied and Environmental Microbiology ◽

10.1128/aem.07738-11 ◽

2012 ◽

Vol 78 (7) ◽

pp. 2456-2458 ◽

Cited By ~ 23

Author(s):

Era Tuladhar ◽

Martijn C. de Koning ◽

Irina Fundeanu ◽

Rijkelt Beumer ◽

Erwin Duizer

Keyword(s):

Influenza Virus ◽

Quaternary Ammonium ◽

Influenza A ◽

H1n1 Virus ◽

Quaternary Ammonium Compounds ◽

Virucidal Activity ◽

Influenza A H1n1 ◽

Virucidal Effect ◽

Plastic Surfaces ◽

Ammonium Compounds

ABSTRACTVirucidal activity of immobilized quaternary ammonium compounds (IQACs) coated onto glass and plastic surfaces was tested against enveloped influenza A (H1N1) virus and nonenveloped poliovirus Sabin1. The IQACs tested were virucidal against the influenza virus within 2 min, but no virucidal effect against poliovirus was found in 6 h.

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Influenza-induced thrombocytopenia is dependent on the subtype and sialoglycan receptor and increases with virus pathogenicity

Blood Advances ◽

10.1182/bloodadvances.2020001640 ◽

2020 ◽

Vol 4 (13) ◽

pp. 2967-2978 ◽

Cited By ~ 4

Author(s):

A. J. Gerard Jansen ◽

Thom Spaan ◽

Hui Zhi Low ◽

Daniele Di Iorio ◽

Judith van den Brand ◽

...

Keyword(s):

Influenza Virus ◽

Platelet Count ◽

Virus Infection ◽

Influenza A ◽

H1n1 Virus ◽

Acute Infection ◽

Influenza Virus Infection ◽

Hepatic Clearance ◽

H3n2 Virus ◽

Influenza A H1n1

Abstract Thrombocytopenia is a common complication of influenza virus infection, and its severity predicts the clinical outcome of critically ill patients. The underlying cause(s) remain incompletely understood. In this study, in patients with an influenza A/H1N1 virus infection, viral load and platelet count correlated inversely during the acute infection phase. We confirmed this finding in a ferret model of influenza virus infection. In these animals, platelet count decreased with the degree of virus pathogenicity varying from 0% in animals infected with the influenza A/H3N2 virus, to 22% in those with the pandemic influenza A/H1N1 virus, up to 62% in animals with a highly pathogenic A/H5N1 virus infection. This thrombocytopenia is associated with virus-containing platelets that circulate in the blood. Uptake of influenza virus particles by platelets requires binding to sialoglycans and results in the removal of sialic acids by the virus neuraminidase, a trigger for hepatic clearance of platelets. We propose the clearance of influenza virus by platelets as a paradigm. These insights clarify the pathophysiology of influenza virus infection and show how severe respiratory infections, including COVID-19, may propagate thrombocytopenia and/or thromboembolic complications.

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