scholarly journals The origins of pandemic influenza ? a perspective

2006 ◽  
Vol 27 (4) ◽  
pp. 177
Author(s):  
Graeme Laver
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
H1n1 Virus ◽  
Influenza Pandemic ◽  
The Other ◽  
H3n2 Virus ◽  
Human Influenza ◽  
Human Influenza Virus ◽  
Influenza Pandemics ◽  
H2n2 Virus

Following the isolation of the first human influenza virus in 1933, there have been two Type A influenza pandemics. One was the Asian influenza pandemic in 1957, when an H2N2 virus replaced the H1N1 viruses then circulating, and the other was in 1968 when the Hong Kong H3N2 virus replaced the H2N2 viruses. The H1N1 virus that re-emerged in 1977 did cause a worldwide epidemic (or pandemic) but this virus is not considered by many people to be a true ?pandemic? virus.

scholarly journals Large-Scale Sequence Analysis of M Gene of Influenza A Viruses from Different Species: Mechanisms for Emergence and Spread of Amantadine Resistance

2009 ◽  
Vol 53 (10) ◽  
pp. 4457-4463 ◽  
Author(s):  
Yuki Furuse ◽  
Akira Suzuki ◽  
Hitoshi Oshitani
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Drug Resistant ◽  
Human Influenza ◽  
Influenza A Viruses ◽  
M Gene ◽  
Drug Pressure ◽  
Human Influenza Virus ◽  
Selective Pressures ◽  
Amantadine Resistance

ABSTRACT Influenza A virus infects many species, and amantadine is used as an antiviral agent. Recently, a substantial increase in amantadine-resistant strains has been reported, most of which have a substitution at amino acid position 31 in the M2 gene. Understanding the mechanism responsible for the emergence and spread of antiviral resistance is important for developing a treatment protocol for seasonal influenza and for deciding on a policy for antiviral stockpiling for pandemic influenza. The present study was conducted to identify the existence of drug pressure on the emergence and spread of amantadine-resistant influenza A viruses. We analyzed data on more than 5,000 virus sequences and constructed a phylogenetic tree to calculate selective pressures on sites in the M2 gene associated with amantadine resistance (positions 26, 27, 30, and 31) among different hosts. The phylogenetic tree revealed that the emergence and spread of the drug-resistant M gene in different hosts and subtypes were independent and not through reassortment. For human influenza virus, positive selection was detected only at position 27. Selective pressures on the sites were not always higher for human influenza virus than for viruses of other hosts. Additionally, selective pressure on position 31 did not increase after the introduction of amantadine. Although there is a possibility of drug pressure on human influenza virus, we could not find positive pressure on position 31. Because the recent rapid increase in drug-resistant virus is associated with the substitution at position 31, the resistance may not be related to drug use.

scholarly journals Swine Influenza Virus PA and Neuraminidase Gene Reassortment into Human H1N1 Influenza Virus Is Associated with an Altered Pathogenic Phenotype Linked to Increased MIP-2 Expression

2015 ◽  
Vol 89 (10) ◽  
pp. 5651-5667 ◽  
Author(s):  
Daniel Dlugolenski ◽  
Les Jones ◽  
Elizabeth Howerth ◽  
David Wentworth ◽  
S. Mark Tompkins ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Sialic Acid ◽  
Influenza A ◽  
H1n1 Virus ◽  
Swine Influenza ◽  
Influenza Viruses ◽  
Pandemic H1n1 ◽  
Human Influenza ◽  
Swine Virus ◽  
Virus Reassortment

ABSTRACTSwine are susceptible to infection by both avian and human influenza viruses, and this feature is thought to contribute to novel reassortant influenza viruses. In this study, the influenza virus reassortment rate in swine and human cells was determined. Coinfection of swine cells with 2009 pandemic H1N1 virus (huH1N1) and an endemic swine H1N2 (A/swine/Illinois/02860/09) virus (swH1N2) resulted in a 23% reassortment rate that was independent of α2,3- or α2,6-sialic acid distribution on the cells. The reassortants had altered pathogenic phenotypes linked to introduction of the swine virus PA and neuraminidase (NA) into huH1N1. In mice, the huH1N1 PA and NA mediated increased MIP-2 expression early postinfection, resulting in substantial pulmonary neutrophilia with enhanced lung pathology and disease. The findings support the notion that swine are a mixing vessel for influenza virus reassortants independent of sialic acid distribution. These results show the potential for continued reassortment of the 2009 pandemic H1N1 virus with endemic swine viruses and for reassortants to have increased pathogenicity linked to the swine virus NA and PA genes which are associated with increased pulmonary neutrophil trafficking that is related to MIP-2 expression.IMPORTANCEInfluenza A viruses can change rapidly via reassortment to create a novel virus, and reassortment can result in possible pandemics. Reassortments among subtypes from avian and human viruses led to the 1957 (H2N2 subtype) and 1968 (H3N2 subtype) human influenza pandemics. Recent analyses of circulating isolates have shown that multiple genes can be recombined from human, avian, and swine influenza viruses, leading to triple reassortants. Understanding the factors that can affect influenza A virus reassortment is needed for the establishment of disease intervention strategies that may reduce or preclude pandemics. The findings from this study show that swine cells provide a mixing vessel for influenza virus reassortment independent of differential sialic acid distribution. The findings also establish that circulating neuraminidase (NA) and PA genes could alter the pathogenic phenotype of the pandemic H1N1 virus, resulting in enhanced disease. The identification of such factors provides a framework for pandemic modeling and surveillance.

scholarly journals THE INCIDENCE OF NEUTRALIZING ANTIBODIES FOR HUMAN INFLUENZA VIRUS IN THE SERUM OF HUMAN INDIVIDUALS OF DIFFERENT AGES

1936 ◽  
Vol 63 (5) ◽  
pp. 655-668 ◽  
Author(s):  
Thomas Francis ◽  
T. P. Magill
Keyword(s):  
Influenza Virus ◽  
Neutralizing Antibodies ◽  
Swine Influenza Virus ◽  
Swine Influenza ◽  
The Other ◽  
Human Influenza ◽  
Complete Protection ◽  
Human Influenza Virus ◽  
Human Sera ◽  
Epidemiological Significance

The results of mouse protection tests with 136 human sera and a strain of human influenza virus are described. After the 1st year of life, the sera of approximately half the individuals tested contained sufficient antibody to furnish complete protection to mice. A much higher percentage of the sera obtained from individuals recently convalescent from influenza exerted a completely protective effect. On the other hand, certain sera protected only partially under the conditions of the tests. The results have been compared with those obtained by Shope in tests done with the same sera against swine influenza virus. The possible epidemiological significance of the results is discussed.

scholarly journals Overexpression of the α-2,6-Sialyltransferase in MDCK Cells Increases Influenza Virus Sensitivity to Neuraminidase Inhibitors

2003 ◽  
Vol 77 (15) ◽  
pp. 8418-8425 ◽  
Author(s):  
Mikhail Matrosovich ◽  
Tatyana Matrosovich ◽  
Jackie Carr ◽  
Noel A. Roberts ◽  
Hans-Dieter Klenk
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Cultured Cells ◽  
Mdck Cells ◽  
Sialic Acids ◽  
Neuraminidase Inhibitors ◽  
Human Influenza ◽  
Oseltamivir Carboxylate ◽  
Human Influenza Virus ◽  
Human Virus

ABSTRACT No reliable cell culture assay is currently available for monitoring human influenza virus sensitivity to neuraminidase inhibitors (NAI). This can be explained by the observation that because of a low concentration of sialyl-α2,6-galactose (Sia[α2,6]Gal)-containing virus receptors in conventional cell lines, replication of human virus isolates shows little dependency on viral neuraminidase. To test whether overexpression of Sia(α2,6)Gal moieties in cultured cells could make them suitable for testing human influenza virus sensitivity to NAI, we stably transfected MDCK cells with cDNA of human 2,6-sialyltransferase (SIAT1). Transfected cells expressed twofold-higher amounts of 6-linked sialic acids and twofold-lower amounts of 3-linked sialic acids than parent MDCK cells as judged by staining with Sambucus nigra agglutinin and Maackia amurensis agglutinin, respectively. After transfection, binding of a clinical human influenza virus isolate was increased, whereas binding of its egg-adapted variant which preferentially bound 3-linked receptors was decreased. The sensitivity of human influenza A and B viruses to the neuraminidase inhibitor oseltamivir carboxylate was substantially improved in the SIAT1-transfected cell line and was consistent with their sensitivity in neuraminidase enzyme assay and with the hemagglutinin (HA) receptor-binding phenotype. MDCK cells stably transfected with SIAT1 may therefore be a suitable system for testing influenza virus sensitivity to NAI.

scholarly journals Residual immunity in older people against the influenza A(H1N1) – recent experience in northern Spain

2009 ◽  
Vol 14 (39) ◽  
Author(s):  
E Pérez-Trallero ◽  
L Piñeiro ◽  
D Vicente ◽  
M Montes ◽  
G Cilla
Keyword(s):  
Pandemic Influenza ◽  
Influenza A ◽  
Seasonal Influenza ◽  
H1n1 Virus ◽  
Influenza Pandemic ◽  
Age Groups ◽  
H3n2 Virus ◽  
Recent Experience ◽  
Northern Spain ◽  
Influenza A H1n1

The 2009 pandemic influenza A(H1N1) virus has a higher incidence in children and young adults, a pattern that has also been reported in seasonal influenza caused by the influenza A(H1N1) virus. We analysed age at infection in symptomatic patients with influenza in the Basque Country (northern Spain), reported through the sentinel influenza surveillance system which monitors 2.2-2.5% of the population. Between September 1999 and August 2009, influenza A(H3N2) or seasonal influenza A(H1N1) was detected in 941 patients, and from April to August 2009, pandemic influenza A(H1N1) was detected in 112 patients. The H3/H1 seasonal influenza ratio was between 3.3 and 3.4 in the under 60 year-olds, but 9.8 in older individuals, suggesting that people born before 1950 have residual immunity against the influenza A H1N1 subtype (both seasonal and pandemic). Introduction In 1957, the Asian influenza pandemic was caused by influenza A(H2N2) virus, which circulated until 1968 when it was displaced by the influenza A(H3N2) virus which was responsible for the Hong Kong pandemic. Before 1957, direct descendants of the influenza A(H1N1) virus that had caused the 1918 pandemic (Spanish flu) had circulated. In 1977, an influenza A(H1N1) strain re-emerged, which, together with the dominant influenza A(H3N2) strain, has been the cause of seasonal human influenza for more than three decades [1]. Despite the prolonged co-circulation of both subtypes, few studies have analysed their ability to affect distinct age groups. The current pandemic influenza A(H1N1) virus, influenza A(H1N1)v, which emerged in the spring of 2009, has spread throughout the world. The aim of this study was to compare the distribution in distinct age groups of infections caused by the two subtypes of seasonal influenza in the past 10 seasons and refer therelate this to recent infections due to influenza A(H1N1)v.

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

2020 ◽  
Vol 4 (13) ◽  
pp. 2967-2978 ◽  
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.

scholarly journals Intranasal Immunization with a Formalin-Inactivated Human Influenza A Virus Whole-Virion Vaccine Alone and Intranasal Immunization with a Split-Virion Vaccine with Mucosal Adjuvants Show Similar Levels of Cross-Protection

2012 ◽  
Vol 19 (7) ◽  
pp. 979-990 ◽  
Author(s):  
Shigefumi Okamoto ◽  
Sumiko Matsuoka ◽  
Nobuyuki Takenaka ◽  
Ahmad M. Haredy ◽  
Takeshi Tanimoto ◽  
...  
Keyword(s):  
Immune Response ◽  
Influenza Virus ◽  
Influenza A ◽  
Protective Efficacy ◽  
Cross Protection ◽  
Human Influenza ◽  
Human Influenza Virus ◽  
Mucosal Adjuvant ◽  
Intranasal Immunization ◽  
The Cross

ABSTRACTThe antigenicity of seasonal human influenza virus changes continuously; thus, a cross-protective influenza vaccine design needs to be established. Intranasal immunization with an influenza split-virion (SV) vaccine and a mucosal adjuvant induces cross-protection; however, no mucosal adjuvant has been assessed clinically. Formalin-inactivated intact human and avian viruses alone (without adjuvant) induce cross-protection against the highly pathogenic H5N1 avian influenza virus. However, it is unknown whether seasonal human influenza formalin-inactivated whole-virion (WV) vaccine alone induces cross-protection against strains within a subtype or in a different subtype of human influenza virus. Furthermore, there are few reports comparing the cross-protective efficacy of the WV vaccine and SV vaccine-mucosal adjuvant mixtures. Here, we found that the intranasal human influenza WV vaccine alone induced both the innate immune response and acquired immune response, resulting in cross-protection against drift variants within a subtype of human influenza virus. The cross-protective efficacy conferred by the WV vaccine in intranasally immunized mice was almost the same as that conferred by a mixture of SV vaccine and adjuvants. The level of cross-protective efficacy was correlated with the cross-reactive neutralizing antibody titer in the nasal wash and bronchoalveolar fluids. However, neither the SV vaccine with adjuvant nor the WV vaccine induced cross-reactive virus-specific cytotoxic T-lymphocyte activity. These results suggest that the intranasal human WV vaccine injection alone is effective against variants within a virus subtype, mainly through a humoral immune response, and that the cross-protection elicited by the WV vaccine and the SV vaccine plus mucosal adjuvants is similar.

scholarly journals An influenza A (H1N1) virus, closely related to swine influenza virus, responsible for a fatal case of human influenza.

1994 ◽  
Vol 68 (4) ◽  
pp. 2051-2058 ◽  
Author(s):  
D E Wentworth ◽  
B L Thompson ◽  
X Xu ◽  
H L Regnery ◽  
A J Cooley ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
H1n1 Virus ◽  
Fatal Case ◽  
Swine Influenza Virus ◽  
Swine Influenza ◽  
Human Influenza ◽  
Influenza A H1n1

scholarly journals Infection of a child in Hong Kong by an influenza A H3N2 virus closely related to viruses circulating in European pigs

2001 ◽  
Vol 82 (6) ◽  
pp. 1397-1406 ◽  
Author(s):  
V. Gregory ◽  
W. Lim ◽  
K. Cameron ◽  
M. Bennett ◽  
S. Marozin ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Hong Kong ◽  
Influenza A ◽  
Southern China ◽  
Influenza Viruses ◽  
H3n2 Virus ◽  
Human Influenza ◽  
Genetic Characteristics ◽  
Source Of Infection ◽  
Human Viruses

Influenza virus A/Hong Kong/1774/99, isolated from a young child with mild influenza, was shown to be similar in its antigenic and genetic characteristics to H3N2 viruses circulating in pigs in Europe during the 1990s and in particular to be closely related to viruses isolated from two children in the Netherlands in 1993. Similar viruses had previously not been identified outside Europe. Although there is little evidence as to how the child contracted the infection, it appears likely that pigs in southern China were the source of infection. Characteristics shared with the European swine viruses include resistance to the anti-influenza drugs amantadine and rimantadine. Thus not only does this incident once again highlight the potential of pigs as a source of novel human influenza viruses, but also indicates the potential for emergence of amantadine-resistant human viruses.

scholarly journals Cross-protective immunity against influenza pH1N1 2009 viruses induced by seasonal influenza A (H3N2) virus is mediated by virus-specific T-cells

2011 ◽  
Vol 92 (10) ◽  
pp. 2339-2349 ◽  
Author(s):  
Marine L. B. Hillaire ◽  
Stella E. van Trierum ◽  
Joost H. C. M. Kreijtz ◽  
Rogier Bodewes ◽  
Martina M. Geelhoed-Mieras ◽  
...  
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
Virus Infection ◽  
Protective Immunity ◽  
Influenza A ◽  
Seasonal Influenza ◽  
H1n1 Virus ◽  
H3n2 Virus ◽  
Influenza A H1n1 ◽  
H1n1 Virus Infection

Influenza A (H1N1) viruses of swine origin were introduced into the human population in 2009 and caused a pandemic. The disease burden in the elderly was relatively low, which was attributed to the presence of cross-reacting serum antibodies in this age group, which were raised against seasonal influenza A (H1N1) viruses that circulated before 1957. It has also been described how infection with heterosubtypic influenza viruses can induce some degree of protection against infection by a novel strain of influenza virus. Here, we assess the extent of protective immunity against infection with the 2009 influenza A (H1N1) pandemic influenza virus that is afforded by infection with a seasonal influenza A (H3N2) virus in mice. Mice that experienced a primary A (H3N2) influenza virus infection displayed reduced weight loss after challenge infection and cleared the 2009 influenza A (H1N1) virus infection more rapidly. To elucidate the correlates of protection of this heterosubtypic immunity to pandemic H1N1 virus infection, adoptive transfer experiments were carried out by using selected post-infection lymphocyte populations. Virus-specific CD8+ T-cells in concert with CD4+ T-cells were responsible for the observed protection. These findings may not only provide an explanation for epidemiological differences in the incidence of severe pandemic H1N1 infections, they also indicate that the induction of cross-reactive virus-specific CD8+ and CD4+ T-cell responses may be a suitable approach for the development of universal influenza vaccines.

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