Contributions of the Avian Influenza Virus HA, NA, and M2 Surface Proteins to the Induction of Neutralizing Antibodies and Protective Immunity

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.

Download Full-text

Contributions of HA1 and HA2 Subunits of Highly Pathogenic Avian Influenza Virus in Induction of Neutralizing Antibodies and Protection in Chickens

Frontiers in Microbiology ◽

10.3389/fmicb.2020.01085 ◽

2020 ◽

Vol 11 ◽

Author(s):

Edris Shirvani ◽

Anandan Paldurai ◽

Berin P. Varghese ◽

Siba K. Samal

Keyword(s):

Influenza Virus ◽

Avian Influenza ◽

Avian Influenza Virus ◽

Neutralizing Antibodies ◽

Highly Pathogenic Avian Influenza ◽

Highly Pathogenic ◽

Pathogenic Avian Influenza ◽

Pathogenic Avian Influenza Virus

Download Full-text

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

Viruses ◽

10.3390/v11010040 ◽

2019 ◽

Vol 11 (1) ◽

pp. 40 ◽

Cited By ~ 1

Author(s):

Mengchan Hao ◽

Shaojie Han ◽

Dan Meng ◽

Rong Li ◽

Jing Lin ◽

...

Keyword(s):

Influenza Virus ◽

Avian Influenza ◽

Avian Influenza Virus ◽

Guinea Pigs ◽

Influenza A ◽

Reverse Genetics ◽

Species Barrier ◽

Airborne Transmission ◽

H9n2 Subtype ◽

Influenza A H1n1

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.

Download Full-text

Reverse genetics based rgH5N2 vaccine provides protection against high dose challenge of H5N1 avian influenza virus in chicken

Microbial Pathogenesis ◽

10.1016/j.micpath.2016.06.011 ◽

2016 ◽

Vol 97 ◽

pp. 172-177 ◽

Cited By ~ 3

Author(s):

S. Bhatia ◽

R. Khandia ◽

R. Sood ◽

S. Bhat ◽

A. Siddiqui ◽

...

Keyword(s):

Influenza Virus ◽

Avian Influenza ◽

Avian Influenza Virus ◽

Reverse Genetics ◽

High Dose ◽

H5n1 Avian Influenza Virus ◽

H5n1 Avian Influenza

Download Full-text

Adaptive amino acid substitutions enable transmission of an H9N2 avian influenza virus in guinea pigs

Scientific Reports ◽

10.1038/s41598-019-56122-6 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Liu Lina ◽

Chen Saijuan ◽

Wang Chengyu ◽

Lu Yuefeng ◽

Dong Shishan ◽

...

Keyword(s):

Influenza Virus ◽

Hong Kong ◽

Amino Acid ◽

Avian Influenza ◽

Avian Influenza Virus ◽

Reverse Genetics ◽

Amino Acid Substitutions ◽

Potential Threat ◽

Pathogenic Avian Influenza Virus ◽

The Impact

AbstractH9N2 is the most prevalent low pathogenic avian influenza virus (LPAIV) in domestic poultry in the world. Two distinct H9N2 poultry lineages, G1-like (A/quail/Hong Kong/G1/97) and Y280-like (A/Duck/Hong Kong/Y280/1997) viruses, are usually associated with binding affinity for both α 2,3 and α 2,6 sialic acid receptors (avian and human receptors), raising concern whether these viruses possess pandemic potential. To explore the impact of mouse adaptation on the transmissibility of a Y280-like virus A/Chicken/Hubei/214/2017(H9N2) (abbreviated as WT), we performed serial lung-to-lung passages of the WT virus in mice. The mouse-adapted variant (MA) exhibited enhanced pathogenicity and advantaged transmissibility after passaging in mice. Sequence analysis of the complete genomes of the MA virus revealed a total of 16 amino acid substitutions. These mutations distributed across 7 segments including PB2, PB1, PA, NP, HA, NA and NS1 genes. Furthermore, we generated a panel of recombinant or mutant H9N2 viruses using reverse genetics technology and confirmed that the PB2 gene governing the increased pathogenicity and transmissibility. The combinations of 340 K and 588 V in PB2 were important in determining the altered features. Our findings elucidate the specific mutations in PB2 contribute to the phenotype differences and emphasize the importance of monitoring the identified amino acid substitutions due to their potential threat to human health.

Download Full-text