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 Oseltamivir-Resistant Influenza A Viruses Are Transmitted Efficiently among Guinea Pigs by Direct Contact but Not by Aerosol

2008 ◽  
Vol 82 (20) ◽  
pp. 10052-10058 ◽  
Author(s):  
Nicole M. Bouvier ◽  
Anice C. Lowen ◽  
Peter Palese
Keyword(s):  
Influenza Virus ◽  
Guinea Pigs ◽  
Direct Contact ◽  
Influenza A ◽  
Influenza Pandemic ◽  
Influenza Viruses ◽  
Transmission Model ◽  
Resistance Mutations ◽  
In Ovo ◽  
Oseltamivir Resistance

ABSTRACT Influenza viruses resistant to the neuraminidase (NA) inhibitor oseltamivir arise under drug selection pressure both in vitro and in vivo. Several mutations in the active site of the viral NA are known to confer relative resistance to oseltamivir, and influenza viruses with certain oseltamivir resistance mutations have been shown to transmit efficiently among cocaged ferrets. However, it is not known whether NA mutations alter aerosol transmission of drug-resistant influenza virus. Here, we demonstrate that recombinant human influenza A/H3N2 viruses without and with oseltamivir resistance mutations (in which NA carries the mutation E119V or the double mutations E119V I222V) have similar in ovo growth kinetics and infectivity in guinea pigs. These viruses also transmit efficiently by the contact route among cocaged guinea pigs, as in the ferret model. However, in an aerosol transmission model, in which guinea pigs are caged separately, the oseltamivir-resistant viruses transmit poorly or not at all; in contrast, the oseltamivir-sensitive virus transmits efficiently even in the absence of direct contact. The present results suggest that oseltamivir resistance mutations reduce aerosol transmission of influenza virus, which could have implications for public health measures taken in the event of an influenza pandemic.

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 Genetics, Receptor Binding, Replication, and Mammalian Transmission of H4 Avian Influenza Viruses Isolated from Live Poultry Markets in China

2015 ◽  
Vol 90 (3) ◽  
pp. 1455-1469 ◽  
Author(s):  
Libin Liang ◽  
Guohua Deng ◽  
Jianzhong Shi ◽  
Shuai Wang ◽  
Qianyi Zhang ◽  
...  
Keyword(s):  
Public Health ◽  
Influenza Virus ◽  
Avian Influenza ◽  
Receptor Binding ◽  
Guinea Pigs ◽  
Direct Contact ◽  
Potential Threat ◽  
The World ◽  
Live Poultry ◽  
Live Poultry Markets

ABSTRACTH4 avian influenza virus (AIV) is one of the most prevalent influenza virus subtypes in the world. However, whether H4 AIVs pose a threat to public health remains largely unclear. Here, we analyzed the phylogenetic relationships, receptor binding properties, replication, and transmissibility in mammals of H4 AIVs isolated from live poultry markets in China between 2009 and 2012. Genomic sequence analysis of 36 representative H4 viruses revealed 32 different genotypes, indicating that these viruses are undergoing complex and frequent reassortment events. All 32 viruses tested could replicate in the respiratory organs of infected mice without prior adaptation. Receptor binding analysis demonstrated that the H4 AIVs bound to α-2,6-linked glycans, although they retained the binding preference for α-2,3-linked glycans. When we tested the direct-contact transmission of 10 H4 viruses in guinea pigs, we found that three viruses did not transmit to any of the contact animals, one virus transmitted to one of three contact animals, and six viruses transmitted to all three contact animals. When we further tested the respiratory droplet transmissibility of four of the viruses that transmitted efficiently via direct contact, we found that three of them could transmit to one or two of the five exposed animals. Our study demonstrates that the current circulating H4 AIVs can infect, replicate in, and transmit to mammalian hosts, thereby posing a potential threat to human health. These findings emphasize the continual need for enhanced surveillance of H4 AIVs.IMPORTANCENumerous surveillance studies have documented the wide distribution of H4 AIVs throughout the world, yet the biological properties of H4 viruses have not been well studied. In this study, we found that multiple genotypes of H4 viruses are cocirculating in the live poultry markets of China and that H4 viruses can replicate in mice, possess human-type receptor binding specificity, and transmit between guinea pigs via direct contact. Strikingly, some H4 strains also can transmit via respiratory droplet, albeit with limited efficiency. These results clearly show the potential threat posed by H4 viruses to public health.

scholarly journals Pandemic H1N1 influenza: predicting the course of a pandemic and assessing the efficacy of the planned vaccination programme in the United States

2009 ◽  
Vol 14 (41) ◽  
Author(s):  
S Towers ◽  
Z Feng
Keyword(s):  
United States ◽  
Influenza A ◽  
Influenza Pandemic ◽  
Vaccination Campaign ◽  
H1n1 Influenza ◽  
The United States ◽  
Pandemic H1n1 ◽  
Pandemic H1n1 Influenza ◽  
Influenza A H1n1 ◽  
Control And Prevention

We use data on confirmed cases of pandemic influenza A(H1N1), disseminated by the United States Centers for Disease Control and Prevention(US CDC), to fit the parameters of a seasonally forced Susceptible, Infective, Recovered (SIR) model. We use the resulting model to predict the course of the H1N1 influenza pandemic in autumn 2009, and we assess the efficacy of the planned CDC H1N1 vaccination campaign. The model predicts that there will be a significant wave in autumn, with 63% of the population being infected, and that this wave will peak so early that the planned CDC vaccination campaign will likely not have a large effect on the total number of people ultimately infected by the pandemic H1N1 influenza virus.

scholarly journals Clinical impact of influenza – lessons learnt from the pandemic influenza A (H1N1) 2009

2011 ◽  
Vol 32 (1) ◽  
pp. 29
Author(s):  
Alex Dierig ◽  
Gulam Khandaker ◽  
Robert Booy
Keyword(s):  
Clinical Features ◽  
Pandemic Influenza ◽  
Influenza A ◽  
Influenza Pandemic ◽  
Gastrointestinal Symptoms ◽  
H1n1 Influenza ◽  
World Health ◽  
Pandemic H1n1 ◽  
Pandemic H1n1 Influenza ◽  
Influenza A H1n1

Influenza is generally an acute, self-limiting, febrile illness without further complications in the majority of people. However, it can be associated with severe morbidity and mortality and the burden of the disease on society is likely to be underestimated. In 2009 an outbreak of H1N1 influenza A virus infection was detected in Mexico with further cases soon observed worldwide. Subsequently, in June 2009, the first influenza pandemic of the 21st century due to influenza A (H1N1) was declared by the World Health Organization (WHO). There were many uncertainties regarding the virulence, clinical symptoms and epidemiological features of this newly evolved influenza A strain. Over time, many similarities, but also some differences between the pandemic H1N1 influenza A and seasonal influenza were identified. We recently performed a systematic review of the literature, looking at articles published between 1 April 2009 and 31 January 2010, to identify the epidemiological and clinical features of the pandemic H1N1 influenza. In this current article we compare our findings with others from the international literature. There was more severe impact on young and healthy adults, children, pregnant women and the obese. Clinical features in general were similar between seasonal and pandemic influenza; however, there were more gastrointestinal symptoms associated with pandemic H1N1 influenza. Shortness of breath was characteristic of more severe pH1N1 2009 infection with a higher possibility of being admitted to an intensive care unit (ICU).

scholarly journals Hospitalizations associated with 2009 influenza A (H1N1) and seasonal influenza in Saurashtra region, India

2010 ◽  
Vol 4 (12) ◽  
pp. 834-841 ◽  
Author(s):  
Rajesh K Chudasama ◽  
Umed V Patel ◽  
Pramod B Verma
Keyword(s):  
Influenza Virus ◽  
Median Time ◽  
Influenza A ◽  
Seasonal Influenza ◽  
H1n1 Influenza ◽  
Pandemic H1n1 ◽  
H1n1 Influenza Virus ◽  
Pandemic H1n1 Influenza ◽  
Influenza A H1n1 ◽  
Epidemiological Characteristics

Introduction: This study investigated the clinico-epidemiological characteristics of patients who were hospitalized with 2009 pandemic H1N1 influenza virus infection and seasonal influenza in the Saurashtra region of India. Methodology: From September 2009 to February 2010, a total of 773 patients with influenza virus attending different hospitals in Rajkot city were studied. Real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) testing was used to confirm infection; the clinico-epidemiological features of the disease were closely monitored. Results: Of the 733 patients, 35.4% (274/773) were cases of 2009 pandemic H1N1 influenza and 64.6% (499/773) were cases of seasonal influenza. Of the 274 patients with 2009 pandemic H1N1 influenza, the median age was 29.5 years, and 51.5% were males. Only 1.1% positive patients had recent travel history to an infected region. A median time of five days was observed from onset of illness to influenza A (H1N1) diagnosis, and a median time of six days was reported for hospital stay. All admitted influenza A (H1N1) patients received Oseltamivir drug, but only 16.1% received it within two days of onset of illness. One fourth of the admitted positive patients died. The most common symptoms were cough, fever, sore throat, and shortness of breath. The coexisting conditions were diabetes mellitus, hypertension, chronic pulmonary diseases, and pregnancy (p = 0.001). Chest radiography revealed 93% of the positive patients had pneumonia. Conclusion: The clinical course and outcomes of the 2009 pandemic (H1N1) influenza virus are comparable to those of the currently circulating seasonal influenza, with high mortality in influenza A (H1N1) patients.

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
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