scholarly journals The PA Subunit of the Influenza Virus Polymerase Complex Affects Replication and Airborne Transmission of the H9N2 Subtype Avian Influenza Virus

Viruses ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 40 ◽  
Author(s):  
Mengchan Hao ◽  
Shaojie Han ◽  
Dan Meng ◽  
Rong Li ◽  
Jing Lin ◽  
...  

The polymerase acidic (PA) protein is the third subunit of the influenza A virus polymerase. In recent years, studies have shown that PA plays an important role in overcoming the host species barrier and host adaptation of the avian influenza virus (AIV). The objective of this study was to elucidate the role of the PA subunit on the replication and airborne transmission of the H9N2 subtype AIV. By reverse genetics, a reassortant rSD01-PA was derived from the H9N2 subtype AIV A/Chicken/Shandong/01/2008 (SD01) by introducing the PA gene from the pandemic influenza A H1N1 virus A/swine/Shandong/07/2011 (SD07). Specific pathogen-free (SPF) chickens and guinea pigs were selected as the animal models for replication and aerosol transmission studies. Results show that rSD01-PA lost the ability of airborne transmission among SPF chickens because of the single substitution of the PA gene. However, rSD01-PA could infect guinea pigs through direct contact, while the parental strain SD01 could not, even though the infection of rSD01-PA could not be achieved through aerosol. In summary, our results indicate that the protein encoded by the PA gene plays a key role in replication and airborne transmission of the H9N2 subtype AIV.

2019 ◽  
Author(s):  
Xiaorong Guo ◽  
Dong Yang ◽  
Ruchun Liu ◽  
Yaman Li ◽  
Qingqing Hu ◽  
...  

Abstract Background: Detecting avian influenza virus has become an important public health strategy for controlling the emerging infectious disease. This study aimed to analyze the efficiency of two surveillance systems in detecting the emerging avian influenza viruses. Methods: A modified influenza surveillance system (ISS) and a new built pneumonia surveillance system (PSS) have been used to monitor the viruses in Changsha City, China. The ISS is based on monitoring outpatients in two sentinel hospitals to detect mild influenza and avian influenza cases, and PSS is based on monitoring inpatients in all 49 hospitals to detect severe and death influenza cases. Results: During the study period, 3551917 outpatients were monitored by the ISS system, among which 126076 were influenza-like illness (ILI) cases, with the ILI% of 3.55%. Totally, 14913 throat swabs were collected by the ISS system, among which 2016 were tested positive of influenza or avian influenza virus. Among the positive results, 621 were H3N2, 135 were seasonal H1N1, 610 were influenza A/H1N1 (pandemic in 2009), 106 were untyped influenza A, 540 were B, 1 was H5N6, 1 was H7N9, and 2 were H9N2 virus. 5491560 inpatient people were monitored by the PSS system, among which 6.61% (362743/5491560) were pneumonia cases. 10.55% (38260/362743) of reported pneumonia was severe or death cases. 3401 throat swab or lower respiratory tract samples were collected, among which 2094 were tested positive of influenza or avian influenza virus. Among the positive results, 78 were H3N2, 17 were seasonal H1N1, 1871 were influenza A/H1N1, 103 were untyped influenza A, 16 were B, 1 was H5N6, and 8 were H7N9 virus. Of 15 avian influenza cases reported from January, 2005 to September, 2016, 26.7% (4/15) were mild cases detected by the ISS system, while 60.0% (9/15) were severe or death cases detected by the PSS system. Two H5N1 severe cases were missed by the ISS system in January, 2009 when the PSS system was not available. Conclusion: The two systems seem to be of high efficiency in detecting the emerging avian influenza viruses but need to be verified in other cities or countries.


2007 ◽  
Vol 4 (1) ◽  
pp. 87-92
Author(s):  
Pan Wei-Qi ◽  
Liu Ming ◽  
Zhang Yun ◽  
Liu Chun-Guo ◽  
Yang Tao ◽  
...  

AbstractAvian influenza virus is acquiring the ability to cross the species barrier between birds and mammals. However, the genetic mechanism of this ability is not well known. We successfully rescued aninfluenza A virusA/Chicken/Guangdong/03 (H5N1), which is highly pathogenic to both SPF chickens and BALB/c mice, by plasmid-based reverse genetics. The rescued virus, R-A/Chicken/Guangdong/03 (R-CG), and the wild-type A/Chicken/Guangdong/03 (W-CG) were found to share similar biological properties, such as in titres of 50% egg infectious dose (EID50), 50% tissue culture infectious dose (TCID50) and intravenous pathogenicity index (IPVI). R-CG, like W-CG, is highly pathogenic in mice following natural route infection. Both R-CG and W-CG viruses can be isolated from many organs of mice such as brain, lung, kidney and spleen. As a result, the constructed R-CG reverse genetic system can be used as a tool in the investigation of the molecular mechanism of infection of the mammalian host by avian influenza virus.


2006 ◽  
Vol 80 (4) ◽  
pp. 1959-1964 ◽  
Author(s):  
Wentao Gao ◽  
Adam C. Soloff ◽  
Xiuhua Lu ◽  
Angela Montecalvo ◽  
Doan C. Nguyen ◽  
...  

ABSTRACT The recent emergence of highly pathogenic avian influenza virus (HPAI) strains in poultry and their subsequent transmission to humans in Southeast Asia have raised concerns about the potential pandemic spread of lethal disease. In this paper we describe the development and testing of an adenovirus-based influenza A virus vaccine directed against the hemagglutinin (HA) protein of the A/Vietnam/1203/2004 (H5N1) (VN/1203/04) strain isolated during the lethal human outbreak in Vietnam from 2003 to 2005. We expressed different portions of HA from a recombinant replication-incompetent adenoviral vector, achieving vaccine production within 36 days of acquiring the virus sequence. BALB/c mice were immunized with a prime-boost vaccine and exposed to a lethal intranasal dose of VN/1203/04 H5N1 virus 70 days later. Vaccination induced both HA-specific antibodies and cellular immunity likely to provide heterotypic immunity. Mice vaccinated with full-length HA were fully protected from challenge with VN/1203/04. We next evaluated the efficacy of adenovirus-based vaccination in domestic chickens, given the critical role of fowl species in the spread of HPAI worldwide. A single subcutaneous immunization completely protected chickens from an intranasal challenge 21 days later with VN/1203/04, which proved lethal to all control-vaccinated chickens within 2 days. These data indicate that the rapid production and subsequent administration of recombinant adenovirus-based vaccines to both birds and high-risk individuals in the face of an outbreak may serve to control the pandemic spread of lethal avian influenza.


2006 ◽  
Vol 135 (3) ◽  
pp. 386-391 ◽  
Author(s):  
M. MASE ◽  
M. ETO ◽  
K. IMAI ◽  
K. TSUKAMOTO ◽  
S. YAMAGUCHI

We characterized eleven H9N2 influenza A viruses isolated from chicken products imported from China. Genetically they were classified into six distinct genotypes, including five already known genotypes and one novel genotype. This suggested that such multiple genotypes of the H9N2 virus have possibly already become widespread and endemic in China. Two isolates have amino-acid substitutions that confer resistance to amantadine in the M2 region, and this supported the evidence that this mutation might be a result of the wide application of amantadine for avian influenza treatment in China. These findings emphasize the importance of surveillance for avian influenza virus in this region, and of quarantining imported chicken products as potential sources for the introduction of influenza virus.


Viruses ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1046 ◽  
Author(s):  
Seon-Ju Yeo ◽  
Duc-Duong Than ◽  
Hong-Seog Park ◽  
Haan Woo Sung ◽  
Hyun Park

A novel avian influenza virus (A/wild duck/Korea/K102/2018) (H2N9) was isolated from wild birds in South Korea in 2018, and phylogenetic and molecular analyses were conducted on complete gene sequences obtained by next-generation sequencing. Phylogenetic analysis indicated that the hemagglutinin (HA) and neuraminidase (NA) genes of the A/wild duck/Korea/K102/2018 (H2N9) virus belonged to the Eurasian countries, whereas other internal genes (polymerase basic protein 1 (PB1), PB2, nucleoprotein (NP), polymerase acidic protein (PA), matrix protein (M), and non-structural protein (NS)) belonged to the East Asian countries. A monobasic amino acid (PQIEPR/GLF) at the HA cleavage site, E627 in the PB2 gene, and no deletion of the stalk region in the NA gene indicated that the A/wild duck/Korea/K102/2018 (H2N9) isolate was a typical low pathogenicity avian influenza (LPAI). Nucleotide sequence similarity analysis of HA revealed that the highest homology (98.34%) is to that of A/duck/Mongolia/482/2015 (H2N3), and amino acid sequence of NA was closely related to that of A/duck/Bangladesh/8987/2010 (H10N9) (96.45%). In contrast, internal genes showed homology higher than 98% compared to those of other isolates derived from duck and wild birds of China or Japan in 2016–2018. The newly isolated A/wild duck/Korea/K102/2018 (H2N9) strain is the first reported avian influenza virus in Korea, and may have evolved from multiple genotypes in wild birds and ducks in Mongolia, China, and Japan.


Viruses ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 203
Author(s):  
Hien Thi Tuong ◽  
Ngoc Minh Nguyen ◽  
Haan Woo Sung ◽  
Hyun Park ◽  
Seon-Ju Yeo

In July 2018, a novel avian influenza virus (A/Mandarin duck/South Korea/KNU18-12/2018(H11N9)) was isolated from Mandarin ducks in South Korea. Phylogenetic and molecular analyses were conducted to characterize the genetic origins of the H11N9 strain. Phylogenetic analysis indicated that eight gene segments of strain H11N9 belonged to the Eurasian lineages. Analysis of nucleotide sequence similarity of both the hemagglutinin (HA) and neuraminidase (NA) genes revealed the highest homology with A/duck/Kagoshima/KU57/2014 (H11N9), showing 97.70% and 98.00% nucleotide identities, respectively. Additionally, internal genes showed homology higher than 98% compared to those of other isolates derived from duck and wild birds. Both the polymerase acidic (PA) and polymerase basic 1 (PB1) genes were close to the H5N3 strain isolated in China; whereas, other internal genes were closely related to that of avian influenza virus in Japan. A single basic amino acid at the HA cleavage site (PAIASR↓GLF), the lack of a five-amino acid deletion (residue 69–73) in the stalk region of the NA gene, and E627 in the polymerase basic 2 (PB2) gene indicated that the A/Mandarin duck/South Korea/KNU18-12/2018(H11N9) isolate was a typical low-pathogenicity avian influenza. In vitro viral replication of H11N9 showed a lower titer than H1N1 and higher than H9N2. In mice, H11N9 showed lower adaptation than H1N1. The novel A/Mandarin duck/South Korea/KNU18-12/2018(H11N9) isolate may have resulted from an unknown reassortment through the import of multiple wild birds in Japan and Korea in approximately 2016–2017, evolving to produce a different H11N9 compared to the previous H11N9 in Korea (2016). Further reassortment events of this virus occurred in PB1 and PA in China-derived strains. These results indicate that Japanese- and Chinese-derived avian influenza contributes to the genetic diversity of A/Mandarin duck/South Korea/KNU18-12/2018(H11N9) in Korea.


2009 ◽  
Vol 84 (5) ◽  
pp. 2408-2420 ◽  
Author(s):  
Baibaswata Nayak ◽  
Sachin Kumar ◽  
Joshua M. DiNapoli ◽  
Anandan Paldurai ◽  
Daniel R. Perez ◽  
...  

ABSTRACT Highly pathogenic avian influenza virus (HPAIV) subtype H5N1 causes severe disease and mortality in poultry. Increased transmission of H5N1 HPAIV from birds to humans is a serious threat to public health. We evaluated the individual contributions of each of the three HPAIV surface proteins, namely, the hemagglutinin (HA), the neuraminidase (NA), and the M2 proteins, to the induction of HPAIV-neutralizing serum antibodies and protective immunity in chickens. Using reverse genetics, three recombinant Newcastle disease viruses (rNDVs) were engineered, each expressing the HA, NA, or M2 protein of H5N1 HPAIV. Chickens were immunized with NDVs expressing a single antigen (HA, NA, and M2), two antigens (HA+NA, HA+M2, and NA+M2), or three antigens (HA+NA+M2). Immunization with HA or NA induced high titers of HPAIV-neutralizing serum antibodies, with the response to HA being greater, thus identifying HA and NA as independent neutralization antigens. M2 did not induce a detectable neutralizing serum antibody response, and inclusion of M2 with HA or NA reduced the magnitude of the response. Immunization with HA alone or in combination with NA induced complete protection against HPAIV challenge. Immunization with NA alone or in combination with M2 did not prevent death following challenge, but extended the time period before death. Immunization with M2 alone had no effect on morbidity or mortality. Thus, there was no indication that M2 is immunogenic or protective. Furthermore, inclusion of NA in addition to HA in a vaccine preparation for chickens may not enhance the high level of protection provided by HA.


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