Pathogenesis of Influenza A(H7N9) Virus in Aged Nonhuman Primates

Abstract The avian influenza A(H7N9) virus has caused high mortality rates in humans, especially in the elderly; however, little is known about the mechanistic basis for this. In the current study, we used nonhuman primates to evaluate the effect of aging on the pathogenicity of A(H7N9) virus. We observed that A(H7N9) virus infection of aged animals (defined as age 20–26 years) caused more severe symptoms than infection of young animals (defined as age 2–3 years). In aged animals, lung inflammation was weak and virus infection was sustained. Although cytokine and chemokine expression in the lungs of most aged animals was lower than that in the lungs of young animals, 1 aged animal showed severe symptoms and dysregulated proinflammatory cytokine and chemokine production. These results suggest that attenuated or dysregulated immune responses in aged animals are responsible for the severe symptoms observed among elderly patients infected with A(H7N9) virus.

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Impact of influenza virus during pregnancy: from disease severity to vaccine efficacy

Future Virology ◽

10.2217/fvl-2020-0024 ◽

2020 ◽

Vol 15 (7) ◽

pp. 441-453

Author(s):

Ana Vazquez-Pagan ◽

Rebekah Honce ◽

Stacey Schultz-Cherry

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Immune Responses ◽

Pregnant Women ◽

Disease Severity ◽

Influenza A ◽

Antiviral Treatment ◽

Influenza Virus Infection ◽

Severe Influenza ◽

The Impact

Pregnant women are among the individuals at the highest risk for severe influenza virus infection. Infection of the mother during pregnancy increases the probability of adverse fetal outcomes such as small for gestational age, preterm birth and fetal death. Animal models of syngeneic and allogeneic mating can recapitulate the increased disease severity observed in pregnant women and are used to define the mechanism(s) of that increased severity. This review focuses on influenza A virus pathogenesis, the unique immunological landscape during pregnancy, the impact of maternal influenza virus infection on the fetus and the immune responses at the maternal–fetal interface. Finally, we summarize the importance of immunization and antiviral treatment in this population and highlight issues that warrant further investigation.

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Rescuing Immunosenescence via Non-Specific Vaccination

Immuno ◽

10.3390/immuno1030015 ◽

2021 ◽

Vol 1 (3) ◽

pp. 231-239

Author(s):

Alexander I. Mosa

Keyword(s):

Immune Responses ◽

The Elderly ◽

Short Review ◽

Functional Markers ◽

Healthy Life ◽

Related Disease ◽

Age Related ◽

Population Vulnerability ◽

Mechanistic Basis ◽

Promising Avenue

Discrepancies in lifespan and healthy-life span are predisposing populations to an increasing burden of age-related disease. Accumulating evidence implicates aging of the immune system, termed immunosenescence, in the pathogenesis of multiple age-related diseases. Moreover, immune dysregulation in the elderly increases vulnerability to infection and dampens pathogen-specific immune responses following vaccination. The health challenges manifesting from these age related deficits have been dramatically exemplified by the current SARS-CoV-2 pandemic. Approaches to either attenuate or reverse functional markers of immunosenescence are therefore urgently needed. Recent evidence suggests systemic immunomodulation via non-specific vaccination with live-attenuated vaccines may be a promising avenue to at least reduce aged population vulnerability to viral infection. This short review describes current understanding of immunosenescence, the historical and mechanistic basis of vaccine-mediated immunomodulation, and the outstanding questions and challenges required for broad adoption.

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Asymptomatic, Mild, and Severe Influenza A(H7N9) Virus Infection in Humans, Guangzhou, China

Emerging Infectious Diseases ◽

10.3201/eid2009.140424 ◽

2014 ◽

Vol 20 (9) ◽

Cited By ~ 19

Author(s):

Zongqiu Chen ◽

Hui Liu ◽

Jianyun Lu ◽

Lei Luo ◽

Kuibiao Li ◽

...

Keyword(s):

Virus Infection ◽

Influenza A ◽

H7n9 Virus ◽

Severe Influenza

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Lower cellular immune responses to influenza A (H3N2) in the elderly

Journal of Medical Virology ◽

10.1002/jmv.21544 ◽

2009 ◽

Vol 81 (8) ◽

pp. 1471-1476 ◽

Cited By ~ 7

Author(s):

Na Jia ◽

Chris Li ◽

Yun-Xi Liu ◽

Jan H. Richardus ◽

Dan Feng ◽

...

Keyword(s):

Immune Responses ◽

Influenza A ◽

The Elderly ◽

Cellular Immune Responses ◽

Cellular Immune

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Human Influenza A(H7N9) Virus Infection Associated with Poultry Farm, Northeastern China

Emerging Infectious Diseases ◽

10.3201/eid2011.140608 ◽

2014 ◽

Vol 20 (11) ◽

pp. 1902-1905 ◽

Cited By ~ 11

Author(s):

Ming Fan ◽

Biao Huang ◽

Ao Wang ◽

Liquan Deng ◽

Donglin Wu ◽

...

Keyword(s):

Virus Infection ◽

Influenza A ◽

Northeastern China ◽

Poultry Farm ◽

H7n9 Virus ◽

Human Influenza

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Live-Animal Markets and Influenza A (H7N9) Virus Infection

New England Journal of Medicine ◽

10.1056/nejmc1306100 ◽

2013 ◽

Vol 368 (24) ◽

pp. 2337-2339 ◽

Cited By ~ 92

Author(s):

Chang-jun Bao ◽

Lun-biao Cui ◽

Ming-hao Zhou ◽

Lei Hong ◽

George F. Gao ◽

...

Keyword(s):

Virus Infection ◽

Influenza A ◽

H7n9 Virus ◽

Live Animal

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SMRT sequencing revealed the diversity and characteristics of defective interfering RNAs in influenza A (H7N9) virus infection

Emerging Microbes & Infections ◽

10.1080/22221751.2019.1611346 ◽

2019 ◽

Vol 8 (1) ◽

pp. 662-674 ◽

Cited By ~ 9

Author(s):

Wing-Yu Lui ◽

Chun-Kit Yuen ◽

Can Li ◽

Wan Man Wong ◽

Pak-Yin Lui ◽

...

Keyword(s):

Virus Infection ◽

Influenza A ◽

H7n9 Virus ◽

Smrt Sequencing

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Identification ofInfluenza A/H7N9 Virus Infection-Related Human Genes Based on Shortest Paths in a Virus-Human Protein Interaction Network

BioMed Research International ◽

10.1155/2014/239462 ◽

2014 ◽

Vol 2014 ◽

pp. 1-11 ◽

Cited By ~ 5

Author(s):

Ning Zhang ◽

Min Jiang ◽

Tao Huang ◽

Yu-Dong Cai

Keyword(s):

Virus Infection ◽

Protein Interaction ◽

Protein Interaction Network ◽

Influenza A ◽

Shortest Paths ◽

Interaction Network ◽

Human Protein ◽

H7n9 Virus ◽

Human Protein Interaction ◽

Human Genes

The recently emergingInfluenza A/H7N9 virus is reported to be able to infect humans and cause mortality. However, viral and host factors associated with the infection are poorly understood. It is suggested by the “guilt by association” rule that interacting proteins share the same or similar functions and hence may be involved in the same pathway. In this study, we developed a computational method to identifyInfluenza A/H7N9 virus infection-related human genes based on this rule from the shortest paths in a virus-human protein interaction network. Finally, we screened out the most significant 20 human genes, which could be the potential infection related genes, providing guidelines for further experimental validation. Analysis of the 20 genes showed that they were enriched in protein binding, saccharide or polysaccharide metabolism related pathways and oxidative phosphorylation pathways. We also compared the results with those from human rhinovirus (HRV) and respiratory syncytial virus (RSV) by the same method. It was indicated that saccharide or polysaccharide metabolism related pathways might be especially associated with the H7N9 infection. These results could shed some light on the understanding of the virus infection mechanism, providing basis for future experimental biology studies and for the development of effective strategies for H7N9 clinical therapies.

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