scholarly journals Molecular Characterizations of Surface Proteins Hemagglutinin and Neuraminidase from Recent H5Nx Avian Influenza Viruses

2016 ◽  
Vol 90 (12) ◽  
pp. 5770-5784 ◽  
Author(s):  
Hua Yang ◽  
Paul J. Carney ◽  
Vasiliy P. Mishin ◽  
Zhu Guo ◽  
Jessie C. Chang ◽  
...  
Keyword(s):  
United States ◽  
Avian Influenza ◽  
The United States ◽  
Influenza Viruses ◽  
Surface Proteins ◽  
Health Concern ◽  
Binding Preference ◽  
Major Surface Proteins ◽  
Recombinant Hemagglutinin ◽  
Major Surface

ABSTRACTDuring 2014, a subclade 2.3.4.4 highly pathogenic avian influenza (HPAI) A(H5N8) virus caused poultry outbreaks around the world. In late 2014/early 2015, the virus was detected in wild birds in Canada and the United States, and these viruses also gave rise to reassortant progeny, composed of viral RNA segments (vRNAs) from both Eurasian and North American lineages. In particular, viruses were found with N1, N2, and N8 neuraminidase vRNAs, and these are collectively referred to as H5Nx viruses. In the United States, more than 48 million domestic birds have been affected. Here we present a detailed structural and biochemical analysis of the surface antigens of H5N1, H5N2, and H5N8 viruses in addition to those of a recent human H5N6 virus. Our results with recombinant hemagglutinin reveal that these viruses have a strict avian receptor binding preference, while recombinantly expressed neuraminidases are sensitive to FDA-approved and investigational antivirals. Although H5Nx viruses currently pose a low risk to humans, it is important to maintain surveillance of these circulating viruses and to continually assess future changes that may increase their pandemic potential.IMPORTANCEThe H5Nx viruses emerging in North America, Europe, and Asia pose a great public health concern. Here we report a molecular and structural study of the major surface proteins of several H5Nx influenza viruses. Our results improve the understanding of these new viruses and provide important information on their receptor preferences and susceptibilities to antivirals, which are central to pandemic risk assessment.

scholarly journals H5N2 Avian Influenza Outbreak in Texas in 2004: the First Highly Pathogenic Strain in the United States in 20 Years?

2005 ◽  
Vol 79 (17) ◽  
pp. 11412-11421 ◽  
Author(s):  
Chang-Won Lee ◽  
David E. Swayne ◽  
Jose A. Linares ◽  
Dennis A. Senne ◽  
David L. Suarez
Keyword(s):  
United States ◽  
Amino Acid ◽  
Avian Influenza ◽  
Cleavage Site ◽  
Basic Amino Acid ◽  
The United States ◽  
Influenza Viruses ◽  
Single Point Mutation ◽  
Highly Pathogenic

ABSTRACT In early 2004, an H5N2 avian influenza virus (AIV) that met the molecular criteria for classification as a highly pathogenic AIV was isolated from chickens in the state of Texas in the United States. However, clinical manifestations in the affected flock were consistent with avian influenza caused by a low-pathogenicity AIV and the representative virus (A/chicken/Texas/298313/04 [TX/04]) was not virulent for experimentally inoculated chickens. The hemagglutinin (HA) gene of the TX/04 isolate was similar in sequence to A/chicken/Texas/167280-4/02 (TX/02), a low-pathogenicity AIV isolate recovered from chickens in Texas in 2002. However, the TX/04 isolate had one additional basic amino acid at the HA cleavage site, which could be attributed to a single point mutation. The TX/04 isolate was similar in sequence to TX/02 isolate in several internal genes (NP, M, and NS), but some genes (PA, PB1, and PB2) had sequence of a clearly different origin. The TX/04 isolate also had a stalk deletion in the NA gene, characteristic of a chicken-adapted AIV. By analyzing viruses constructed by in vitro mutagenesis followed by reverse genetics, we found that the pathogenicity of the TX/04 virus could be increased in vitro and in vivo by the insertion of an additional basic amino acid at the HA cleavage site and not by the loss of a glycosylation site near the cleavage site. Our study provides the genetic and biologic characteristics of the TX/04 isolate, which highlight the complexity of the polygenic nature of the virulence of influenza viruses.

scholarly journals Structural and Molecular Characterization of the Hemagglutinin from the Fifth-Epidemic-Wave A(H7N9) Influenza Viruses

2018 ◽  
Vol 92 (16) ◽  
Author(s):  
Hua Yang ◽  
Paul J. Carney ◽  
Jessie C. Chang ◽  
Zhu Guo ◽  
James Stevens
Keyword(s):  
Public Health ◽  
Avian Influenza ◽  
Influenza A ◽  
Human Infection ◽  
Influenza Viruses ◽  
Surface Proteins ◽  
Health Concern ◽  
Public Health Concern ◽  
H7n9 Influenza ◽  
Epidemic Wave

ABSTRACTThe avian influenza A(H7N9) virus continues to cause human infections in China and is a major ongoing public health concern. Five epidemic waves of A(H7N9) infection have occurred since 2013, and the recent fifth epidemic wave saw the emergence of two distinct lineages with elevated numbers of human infection cases and broader geographic distribution of viral diseases compared to the first four epidemic waves. Moreover, highly pathogenic avian influenza (HPAI) A(H7N9) viruses were also isolated during the fifth epidemic wave. Here, we present a detailed structural and biochemical analysis of the surface hemagglutinin (HA) antigen from viruses isolated during this recent epidemic wave. Results highlight that, compared to the 2013 virus HAs, the fifth-wave virus HAs remained a weak binder to human glycan receptor analogs. We also studied three mutations, V177K-K184T-G219S, that were recently reported to switch a 2013 A(H7N9) HA to human-type receptor specificity. Our results indicate that these mutations could also switch the H7 HA receptor preference to a predominantly human binding specificity for both fifth-wave H7 HAs analyzed in this study.IMPORTANCEThe A(H7N9) viruses circulating in China are of great public health concern. Here, we report a molecular and structural study of the major surface proteins from several recent A(H7N9) influenza viruses. Our results improve the understanding of these evolving viruses and provide important information on their receptor preference that is central to ongoing pandemic risk assessment.

scholarly journals Antiviral Susceptibility of Variant Influenza A(H3N2)v Viruses Isolated in the United States from 2011 to 2013

2014 ◽  
Vol 58 (4) ◽  
pp. 2045-2051 ◽  
Author(s):  
K. Sleeman ◽  
V. P. Mishin ◽  
Z. Guo ◽  
R. J. Garten ◽  
A. Balish ◽  
...  
Keyword(s):  
United States ◽  
Influenza A ◽  
Untreated Patient ◽  
Continuous Monitoring ◽  
The United States ◽  
Antiviral Drugs ◽  
Influenza Viruses ◽  
Health Concern ◽  
Public Health Concern ◽  
M Gene

ABSTRACTSince 2011, outbreaks caused by influenza A(H3N2) variant [A(H3N2)v] viruses have become a public health concern in the United States. The A(H3N2)v viruses share the A(H1N1)pdm09 M gene containing the marker of M2 blocker resistance, S31N, but do not contain any known molecular markers associated with resistance to neuraminidase (NA) inhibitors (NAIs). Using a fluorescent NA inhibition (NI) assay, the susceptibilities of recovered A(H3N2)v viruses (n= 168) to FDA-approved (oseltamivir and zanamivir) and other (peramivir, laninamivir, and A-315675) NAIs were assessed. All A(H3N2)v viruses tested, with the exception of a single virus strain, A/Ohio/88/2012, isolated from an untreated patient, were susceptible to the NAIs tested. The A/Ohio/88/2012 virus contained two rare substitutions, S245N and S247P, in the NA and demonstrated reduced inhibition by oseltamivir (31-fold) and zanamivir (66-fold) in the NI assay. Using recombinant NA (recNA) proteins, S247P was shown to be responsible for the observed altered NAI susceptibility, in addition to an approximately 60% reduction in NA enzymatic activity. The S247P substitution has not been previously reported as a molecular marker of reduced susceptibility to the NAIs. Using cell culture assays, the investigational antiviral drugs nitazoxanide, favipiravir, and fludase were shown to inhibit the replication of A(H3N2)v viruses, including the virus with the S247P substitution in the NA. This report demonstrates the importance of continuous monitoring of susceptibility of zoonotic influenza viruses to available and investigational antiviral drugs.

Isolation of H5 Avian Influenza Viruses from Waterfowl in the Upper Midwest Region of the United States

2011 ◽  
Vol 6 (2) ◽  
pp. e15-e16
Author(s):  
Mohamed E. El Zowalaty ◽  
Martha Abin ◽  
Yogesh Chander ◽  
Patrick T. Redig ◽  
Sagar M. Goyal
Keyword(s):  
United States ◽  
Avian Influenza ◽  
The United States ◽  
Influenza Viruses ◽  
Upper Midwest ◽  
Avian Influenza Viruses ◽  
Midwest Region

scholarly journals Structural and Functional Analysis of Surface Proteins from an A(H3N8) Influenza Virus Isolated from New England Harbor Seals

2014 ◽  
Vol 89 (5) ◽  
pp. 2801-2812 ◽  
Author(s):  
Hua Yang ◽  
Ha T. Nguyen ◽  
Paul J. Carney ◽  
Zhu Guo ◽  
Jessie C. Chang ◽  
...  
Keyword(s):  
Influenza Virus ◽  
New England ◽  
Receptor Binding ◽  
Influenza Virus Infection ◽  
Influenza Viruses ◽  
Surface Proteins ◽  
Harbor Seals ◽  
Binding Studies ◽  
Binding Preference ◽  
Major Surface

ABSTRACTIn late 2011, an A(H3N8) influenza virus infection resulted in the deaths of 162 New England harbor seals. Virus sequence analysis and virus receptor binding studies highlighted potential markers responsible for mammalian adaptation and a mixed receptor binding preference (S. J. Anthony, J. A. St Leger, K. Pugliares, H. S. Ip, J. M. Chan, Z. W. Carpenter, I. Navarrete-Macias, M. Sanchez-Leon, J. T. Saliki, J. Pedersen, W. Karesh, P. Daszak, R. Rabadan, T. Rowles, W. I. Lipkin, MBio 3:e00166-00112, 2012,http://dx.doi.org/10.1128/mBio.00166-12). Here, we present a detailed structural and biochemical analysis of the surface antigens of the virus. Results obtained with recombinant proteins for both the hemagglutinin and neuraminidase indicate a true avian receptor binding preference. Although the detection of this virus in new species highlights an increased potential for cross-species transmission, our results indicate that the A(H3N8) virus currently poses a low risk to humans.IMPORTANCECross-species transmission of zoonotic influenza viruses increases public health concerns. Here, we report a molecular and structural study of the major surface proteins from an A(H3N8) influenza virus isolated from New England harbor seals. The results improve our understanding of these viruses as they evolve and provide important information to aid ongoing risk assessment analyses as these zoonotic influenza viruses continue to circulate and adapt to new hosts.

scholarly journals The Pathobiology of H7N3 Low and High Pathogenicity Avian Influenza Viruses from the United States Outbreak in 2020 Differs between Turkeys and Chickens

Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1851
Author(s):  
Miriã F. Criado ◽  
Christina M. Leyson ◽  
Sungsu Youk ◽  
Suzanne DeBlois ◽  
Tim Olivier ◽  
...  
Keyword(s):  
United States ◽  
Influenza Virus ◽  
South Carolina ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
The United States ◽  
Influenza Viruses ◽  
Infectious Dose ◽  
High Pathogenicity ◽  
Commercial Turkey

An outbreak caused by H7N3 low pathogenicity avian influenza virus (LPAIV) occurred in commercial turkey farms in the states of North Carolina (NC) and South Carolina (SC), United States in March of 2020. Subsequently, H7N3 high pathogenicity avian influenza virus (HPAIV) was detected on a turkey farm in SC. The infectivity, transmissibility, and pathogenicity of the H7N3 HPAIV and two LPAIV isolates, including one with a deletion in the neuraminidase (NA) protein stalk, were studied in turkeys and chickens. High infectivity [<2 log10 50% bird infectious dose (BID50)] and transmission to birds exposed by direct contact were observed with the HPAIV in turkeys. In contrast, the HPAIV dose to infect chickens was higher than for turkeys (3.7 log10 BID50), and no transmission was observed. Similarly, higher infectivity (<2–2.5 log10 BID50) and transmissibility were observed with the H7N3 LPAIVs in turkeys compared to chickens, which required higher virus doses to become infected (5.4–5.7 log10 BID50). The LPAIV with the NA stalk deletion was more infectious in turkeys but did not have enhanced infectivity in chickens. These results show clear differences in the pathobiology of AIVs in turkeys and chickens and corroborate the high susceptibility of turkeys to both LPAIV and HPAIV infections.

Isolation of H5 Avian Influenza Viruses from Waterfowl in the Upper Midwest Region of the United States

2011 ◽  
Vol 55 (2) ◽  
pp. 259-262 ◽  
Author(s):  
Mohamed E. El Zowalaty ◽  
Martha Abin ◽  
Yogesh Chander ◽  
Patrick T. Redig ◽  
Sagar M. Goyal
Keyword(s):  
United States ◽  
Avian Influenza ◽  
The United States ◽  
Influenza Viruses ◽  
Upper Midwest ◽  
Avian Influenza Viruses ◽  
Midwest Region
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