scholarly journals Transmission of Pandemic H1N1 Influenza Virus and Impact of Prior Exposure to Seasonal Strains or Interferon Treatment

2009 ◽  
Vol 84 (1) ◽  
pp. 21-26 ◽  
Author(s):  
John Steel ◽  
Peter Staeheli ◽  
Samira Mubareka ◽  
Adolfo García-Sastre ◽  
Peter Palese ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Guinea Pigs ◽  
Influenza Pandemic ◽  
H1n1 Influenza ◽  
Influenza Viruses ◽  
Prior Exposure ◽  
Pandemic H1n1 ◽  
H1n1 Strain ◽  
H3n2 Influenza ◽  
The Impact

ABSTRACT Novel swine-origin influenza viruses of the H1N1 subtype were first detected in humans in April 2009. As of 12 August 2009, 180,000 cases had been reported globally. Despite the fact that they are of the same antigenic subtype as seasonal influenza viruses circulating in humans since 1977, these viruses continue to spread and have caused the first influenza pandemic since 1968. Here we show that a pandemic H1N1 strain replicates in and transmits among guinea pigs with similar efficiency to that of a seasonal H3N2 influenza virus. This transmission was, however, partially disrupted when guinea pigs had preexisting immunity to recent human isolates of either the H1N1 or H3N2 subtype and was fully blocked through daily intranasal administration of interferon to either inoculated or exposed animals. Our results suggest that partial immunity resulting from prior exposure to conventional human strains may blunt the impact of pandemic H1N1 viruses in the human population. In addition, the use of interferon as an antiviral prophylaxis may be an effective way to limit spread in at-risk populations.

scholarly journals Adaptive Mutations That Occurred during Circulation in Humans of H1N1 Influenza Virus in the 2009 Pandemic Enhance Virulence in Mice

2015 ◽  
Vol 89 (14) ◽  
pp. 7329-7337 ◽  
Author(s):  
A. Otte ◽  
M. Sauter ◽  
M. A. Daxer ◽  
A. C. McHardy ◽  
K. Klingel ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Molecular Mechanisms ◽  
Influenza Pandemic ◽  
H1n1 Influenza ◽  
Influenza Viruses ◽  
Pandemic H1n1 ◽  
Adaptive Mutations ◽  
Pandemic H1n1 Influenza ◽  
Viral Hemagglutinin

ABSTRACTDuring the 2009 H1N1 influenza pandemic, infection attack rates were particularly high among young individuals who suffered from pneumonia with occasional death. Moreover, previously reported determinants of mammalian adaptation and pathogenicity were not present in 2009 pandemic H1N1 influenza A viruses. Thus, it was proposed that unknown viral factors might have contributed to disease severity in humans. In this study, we performed a comparative analysis of two clinical 2009 pandemic H1N1 strains that belong to the very early and later phases of the pandemic. We identified mutations in the viral hemagglutinin (HA) and the nucleoprotein (NP) that occurred during pandemic progression and mediate increased virulence in mice. Lethal disease outcome correlated with elevated viral replication in the alveolar epithelium, increased proinflammatory cytokine and chemokine responses, pneumonia, and lymphopenia in mice. These findings show that viral mutations that have occurred during pandemic circulation among humans are associated with severe disease in mice.IMPORTANCEIn this study, novel determinants of 2009 pandemic H1N1 influenza pathogenicity were identified in the viral hemagglutinin (HA) and the nucleoprotein (NP) genes. In contrast to highly pathogenic avian influenza viruses, increased virulence in mice did not correlate with enhanced polymerase activity but with reduced activity. Lethal 2009 pandemic H1N1 infection in mice correlated with lymphopenia and severe pneumonia. These studies suggest that molecular mechanisms that mediate 2009 pandemic H1N1 influenza pathogenicity are distinct from those that mediate avian influenza virus pathogenicity in mice.

scholarly journals Two amino acid substitutions in the haemagglutinin of the 2009 pandemic H1N1 virus decrease direct-contact transmission in guinea pigs

2014 ◽  
Vol 95 (12) ◽  
pp. 2612-2617 ◽  
Author(s):  
Liang He ◽  
Kaijun Jiang ◽  
Qiwen Wu ◽  
Zhiqiang Duan ◽  
Haixu Xu ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Receptor Binding ◽  
Guinea Pigs ◽  
Direct Contact ◽  
Influenza A ◽  
Influenza Pandemic ◽  
H1n1 Influenza ◽  
Pandemic H1n1 ◽  
Binding Preference ◽  
Contact Transmission

The 2009 pandemic H1N1 influenza A virus spread across the globe and caused the first influenza pandemic of the 21st century. Many of the molecular factors that contributed to the airborne transmission of this pandemic virus have been determined; however, the direct-contact transmission of this virus remains poorly understood. In this study, we report that a combination of two mutations (N159D and Q226R) in the haemagglutinin (HA) protein of the representative 2009 H1N1 influenza virus A/California/04/2009 (CA04) caused a switch in receptor binding preference from the α2,6-sialoglycan to the α2,3-sialoglycan receptor, and decreased the binding intensities for both glycans. In conjunction with a significantly decreased replication efficiency in the nasal epithelium, this limited human receptor binding affinity resulted in inefficient direct-contact transmission of CA04 between guinea pigs. Our findings highlight the role of the HA gene in the transmission of the influenza virus.

scholarly journals Genetic and Pathobiologic Characterization of Pandemic H1N1 2009 Influenza Viruses from a Naturally Infected Swine Herd

2009 ◽  
Vol 84 (5) ◽  
pp. 2245-2256 ◽  
Author(s):  
Hana M. Weingartl ◽  
Yohannes Berhane ◽  
Tamiko Hisanaga ◽  
James Neufeld ◽  
Helen Kehler ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Viral Evolution ◽  
H1n1 Influenza ◽  
The United States ◽  
Human Case ◽  
Influenza Viruses ◽  
Viral Rna ◽  
Pandemic H1n1 ◽  
H1n1 Influenza Virus ◽  
Live Virus

ABSTRACT Since its initial identification in Mexico and the United States, concerns have been raised that the novel H1N1 influenza virus might cause a pandemic of severity comparable to that of the 1918 pandemic. In late April 2009, viruses phylogenetically related to pandemic H1N1 influenza virus were isolated from an outbreak on a Canadian pig farm. This outbreak also had epidemiological links to a suspected human case. Experimental infections carried out in pigs using one of the swine isolates from this outbreak and the human isolate A/Mexico/InDRE4487/2009 showed differences in virus recovery from the lower respiratory tract. Virus was consistently isolated from the lungs of pigs infected with A/Mexico/InDRE4487/2009, while only one pig infected with A/swine/Alberta/OTH-33-8/2008 yielded live virus from the lung, despite comparable amounts of viral RNA and antigen in both groups of pigs. Clinical disease resembled other influenza virus infections in swine, albeit with somewhat prolonged virus antigen detection and delayed viral-RNA clearance from the lungs. There was also a noteworthy amount of genotypic variability among the viruses isolated from the pigs on the farm. This, along with the somewhat irregular pathobiological characteristics observed in experimentally infected animals, suggests that although the virus may be of swine origin, significant viral evolution may still be ongoing.

scholarly journals Zanamivir, at 600 Milligrams Twice Daily, Inhibits Oseltamivir-Resistant 2009 Pandemic H1N1 Influenza Virus in anIn VitroHollow-Fiber Infection Model System

2011 ◽  
Vol 55 (4) ◽  
pp. 1740-1746 ◽  
Author(s):  
Ashley N. Brown ◽  
James J. McSharry ◽  
Qingmei Weng ◽  
Jonathan R. Adams ◽  
Robert Kulawy ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
H1n1 Influenza ◽  
Model System ◽  
Hospitalized Patients ◽  
Influenza Viruses ◽  
Infection Model ◽  
Pandemic H1n1 ◽  
The Government

ABSTRACTIn 2009, a novel H1N1 influenza A virus emerged and spread worldwide, initiating a pandemic. Various isolates obtained from disparate parts of the world were shown to be uniformly resistant to the adamantanes but sensitive to the neuraminidase inhibitors oseltamivir and zanamivir. Over time, resistance to oseltamivir became more prevalent among pandemic H1N1 virus isolates, while most remained susceptible to zanamivir. The government has proposed the use of intravenous (i.v.) zanamivir to treat serious influenza virus infections among hospitalized patients. To use zanamivir effectively for patients with severe influenza, it is necessary to know the optimal dose and schedule of administration of zanamivir that will inhibit the replication of oseltamivir-sensitive and -resistant influenza viruses. Therefore, we performed studies using thein vitrohollow-fiber infection model system to predict optimal dosing regimens for zanamivir against an oseltamivir-sensitive and an oseltamivir-resistant virus. Our results demonstrated that zanamivir, at a dose of 600 mg given twice a day (Q12h), inhibited the replication of oseltamivir-sensitive and oseltamivir-resistant influenza viruses throughout the course of the experiment. Thus, our findings suggest that intravenous zanamivir, at a dose of 600 mg Q12h, could be used to treat hospitalized patients suffering from serious infections with oseltamivir-sensitive or -resistant influenza viruses.

scholarly journals Pathogenesis of Infection with 2009 Pandemic H1N1 Influenza Virus in Isogenic Guinea Pigs after Intranasal or Intratracheal Inoculation

2015 ◽  
Vol 185 (3) ◽  
pp. 643-650 ◽  
Author(s):  
Lidewij C.M. Wiersma ◽  
Stella E. Vogelzang-van Trierum ◽  
Geert van Amerongen ◽  
Peter van Run ◽  
Nella J. Nieuwkoop ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Guinea Pigs ◽  
H1n1 Influenza ◽  
Pandemic H1n1 ◽  
H1n1 Influenza Virus ◽  
Pandemic H1n1 Influenza

Emergence and characterisation of pandemic H1N1 influenza viruses in Hungarian swine herds

2013 ◽  
Vol 61 (1) ◽  
pp. 125-134 ◽  
Author(s):  
Ádám Bálint ◽  
István Kiss ◽  
Krisztián Bányai ◽  
Imre Biksi ◽  
Katalin Szentpáli-Gavallér ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Amino Acid ◽  
H1n1 Influenza ◽  
Influenza Viruses ◽  
Viral Fitness ◽  
Pandemic H1n1 ◽  
H1n1 Influenza Virus ◽  
Pandemic H1n1 Influenza ◽  
Molecular Features ◽  
Swine Herds

In 2010, two novel porcine H1N1 influenza viruses were isolated from pigs with influenza-like illness in Hungarian swine herds. Sequence and phylogenetic analysis of these strains revealed that they shared molecular features with the pandemic H1N1 influenza virus strains, which emerged globally during 2009. The PB2, HA and NA genes contained unique amino acid changes compared to the available new H1N1 influenza virus sequences of pig origin. Furthermore, the investigated strains could be separated with respect to parallel amino acid substitutions affecting the polymerase genes (PB2, PB1 and PA) and the nucleoprotein (NP) gene, supporting the proposed complementarities between these proteins, all required for the viral fitness. Molecular characterisation of two Hungarian human pandemic H1N1 isolates was also performed, so that we could compare contemporaneous strains of different host species origins. Shared molecular motifs in various genes of animal and human influenza strains suggested that the Hungarian porcine strains could have originated from humans through direct interspecies transmission. This study is among the few that support the natural human-to-pig transmission of the pandemic H1N1 influenza virus.

scholarly journals Swine Influenza H1N1 Virus Induces Acute Inflammatory Immune Responses in Pig Lungs: a Potential Animal Model for Human H1N1 Influenza Virus

2010 ◽  
Vol 84 (21) ◽  
pp. 11210-11218 ◽  
Author(s):  
Mahesh Khatri ◽  
Varun Dwivedi ◽  
Steven Krakowka ◽  
Cordelia Manickam ◽  
Ahmed Ali ◽  
...  
Keyword(s):  
Animal Model ◽  
T Cells ◽  
Influenza Virus ◽  
Immune Responses ◽  
Swine Influenza ◽  
H1n1 Influenza ◽  
Influenza Viruses ◽  
Nasal Discharge ◽  
Pandemic H1n1 ◽  
H1n1 Influenza Virus

ABSTRACT Pigs are capable of generating reassortant influenza viruses of pandemic potential, as both the avian and mammalian influenza viruses can infect pig epithelial cells in the respiratory tract. The source of the current influenza pandemic is H1N1 influenza A virus, possibly of swine origin. This study was conducted to understand better the pathogenesis of H1N1 influenza virus and associated host mucosal immune responses during acute infection in humans. Therefore, we chose a H1N1 swine influenza virus, Sw/OH/24366/07 (SwIV), which has a history of transmission to humans. Clinically, inoculated pigs had nasal discharge and fever and shed virus through nasal secretions. Like pandemic H1N1, SwIV also replicated extensively in both the upper and lower respiratory tracts, and lung lesions were typical of H1N1 infection. We detected innate, proinflammatory, Th1, Th2, and Th3 cytokines, as well as SwIV-specific IgA antibody in lungs of the virus-inoculated pigs. Production of IFN-γ by lymphocytes of the tracheobronchial lymph nodes was also detected. Higher frequencies of cytotoxic T lymphocytes, γδ T cells, dendritic cells, activated T cells, and CD4+ and CD8+ T cells were detected in SwIV-infected pig lungs. Concomitantly, higher frequencies of the immunosuppressive T regulatory cells were also detected in the virus-infected pig lungs. The findings of this study have relevance to pathogenesis of the pandemic H1N1 influenza virus in humans; thus, pigs may serve as a useful animal model to design and test effective mucosal vaccines and therapeutics against influenza virus.

Sign in / Sign up

Export Citation Format

Share Document