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高致病性禽流感病毒HA1和HA2亚基在诱导鸡产生中和抗体及提供保护方面的作用

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

作者信息

Shirvani Edris, Paldurai Anandan, Varghese Berin P, Samal Siba K

机构信息

Virginia-Maryland College of Veterinary Medicine, University of Maryland, College Park, College Park, MD, United States.

出版信息

Front Microbiol. 2020 Jun 5;11:1085. doi: 10.3389/fmicb.2020.01085. eCollection 2020.

DOI:10.3389/fmicb.2020.01085
PMID:32582071
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7291869/
Abstract

Highly pathogenic avian influenza virus (HPAIV) subtype H5N1 causes a devastating disease in poultry. Vaccination is an effective method of controlling avian influenza virus (AIV) infection in poultry. The hemagglutinin (HA) protein is the major determinant recognized by the immune system of the host. Cleavage of the HA precursor HA0 into HA1 and HA2 subunits is required for infectivity of the AIV. We evaluated the individual contributions of HA1 and HA2 subunits to the induction of HPAIV serum neutralizing antibodies and protective immunity in chickens. Using reverse genetics, recombinant Newcastle disease viruses (rNDVs) were generated, each expressing HA1, HA2, or HA protein of H5N1 HPAIV. Chickens were immunized with rNDVs expressing HA1, HA2, or HA. Immunization with HA induced high titers of serum neutralizing antibodies and prevented death following challenge. Immunization with HA1 or HA2 alone neither induced serum neutralizing antibodies nor prevented death following challenge. Our results suggest that interaction of HA1 and HA2 subunits is necessary for the display of epitopes on HA protein involved in the induction of neutralizing antibodies and protection. These epitopes are lost when the two subunits are separated. Therefore, vaccination with either a HA1 or HA2 subunit may not provide protection against HPAIV.

摘要

高致病性禽流感病毒（HPAIV）H5N1亚型在家禽中引发毁灭性疾病。疫苗接种是控制家禽感染禽流感病毒（AIV）的有效方法。血凝素（HA）蛋白是宿主免疫系统识别的主要决定因素。AIV的感染性需要将HA前体HA0裂解为HA1和HA2亚基。我们评估了HA1和HA2亚基对诱导鸡体内HPAIV血清中和抗体及保护性免疫的个体贡献。利用反向遗传学技术，构建了重组新城疫病毒（rNDV），每个rNDV分别表达H5N1 HPAIV的HA1、HA2或HA蛋白。用表达HA1、HA2或HA的rNDV免疫鸡。用HA免疫可诱导产生高滴度的血清中和抗体，并在攻毒后预防死亡。单独用HA1或HA2免疫既不诱导血清中和抗体，也不能在攻毒后预防死亡。我们的结果表明，HA1和HA2亚基的相互作用对于展示HA蛋白上参与诱导中和抗体及保护作用的表位是必要的。当两个亚基分离时，这些表位会丢失。因此，用HA1或HA2亚基进行疫苗接种可能无法提供针对HPAIV的保护。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d74/7291869/eddb9d88578c/fmicb-11-01085-g006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d74/7291869/d9935cf594e5/fmicb-11-01085-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d74/7291869/c235d1bfb5c9/fmicb-11-01085-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d74/7291869/eddb9d88578c/fmicb-11-01085-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d74/7291869/a5062e23b37c/fmicb-11-01085-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d74/7291869/f2cef647e341/fmicb-11-01085-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d74/7291869/2b2a963c28be/fmicb-11-01085-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d74/7291869/d9935cf594e5/fmicb-11-01085-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d74/7291869/c235d1bfb5c9/fmicb-11-01085-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d74/7291869/eddb9d88578c/fmicb-11-01085-g006.jpg

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