SnapShot: Evolution of Human Influenza A Viruses

Wendel, Isabel; Matrosovich, Mikhail; Klenk, Hans Dieter

doi:10.1016/j.chom.2015.02.001

Cited by 11 publications

(8 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Influenza A virus (IAV) causes acute respiratory tract infection and is a significant human pathogen causing annual epidemics and periodic pandemics ( 1 ). Annual influenza epidemics are caused by circulating “seasonal” influenza viruses, which currently include H1N1 and H3N2 subtype IAVs and influenza B viruses.…”

Section: Introductionmentioning

confidence: 99%

Balancing Immune Protection and Immune Pathology by CD8+ T-Cell Responses to Influenza Infection

2016

View full text Add to dashboard Cite

Influenza A virus (IAV) is a significant human pathogen causing annual epidemics and periodic pandemics. CD8+ cytotoxic T lymphocyte (CTL)-mediated immunity contributes to the clearance of virus-infected cells, and CTL immunity targeting the conserved internal proteins of IAVs is a key protection mechanism when neutralizing antibodies are absent during heterosubtypic IAV infection. However, CTL infiltration into the airways, its cytotoxicity, and the effects of produced proinflammatory cytokines can cause severe lung tissue injury, thereby contributing to immunopathology. Studies have discovered complicated and exquisite stimulatory and inhibitory mechanisms that regulate CTL magnitude and effector activities during IAV infection. Here, we review the state of knowledge on the roles of IAV-specific CTLs in immune protection and immunopathology during IAV infection in animal models, highlighting the key findings of various requirements and constraints regulating the balance of immune protection and pathology involved in CTL immunity. We also discuss the evidence of cross-reactive CTL immunity as a positive correlate of cross-subtype protection during secondary IAV infection in both animal and human studies. We argue that the effects of CTL immunity on protection and immunopathology depend on multiple layers of host and viral factors, including complex host mechanisms to regulate CTL magnitude and effector activity, the pathogenic nature of the IAV, the innate response milieu, and the host historical immune context of influenza infection. Future efforts are needed to further understand these key host and viral factors, especially to differentiate those that constrain optimally effective CTL antiviral immunity from those necessary to restrain CTL-mediated non-specific immunopathology in the various contexts of IAV infection, in order to develop better vaccination and therapeutic strategies for modifying protective CTL immunity.

show abstract

Section: Introductionmentioning

confidence: 99%

Balancing Immune Protection and Immune Pathology by CD8+ T-Cell Responses to Influenza Infection

2016

View full text Add to dashboard Cite

show abstract

“…During the past century, more than ten of the avian virus subtypes were also infectious in humans [ 6 ]. Three (H1N1, H2N2, and H3N2) were capable of human-to-human (H2H) transmission and the cause of world-wide pandemics [ 4 , 7 ]. The initial H1N1 Spanish flu of 1918/1919 claimed over 40 million lives [ 2 , 7 , 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Avian Influenza H7N9 Virus Adaptation to Human Hosts

Tan

Sjaugi

Fong

et al. 2021

Viruses

View full text Add to dashboard Cite

Avian influenza virus A (H7N9), after circulating in avian hosts for decades, was identified as a human pathogen in 2013. Herein, amino acid substitutions possibly essential for human adaptation were identified by comparing the 4706 aligned overlapping nonamer position sequences (1–9, 2–10, etc.) of the reported 2014 and 2017 avian and human H7N9 datasets. The initial set of virus sequences (as of year 2014) exhibited a total of 109 avian-to-human (A2H) signature amino acid substitutions. Each represented the most prevalent substitution at a given avian virus nonamer position that was selectively adapted as the corresponding index (most prevalent sequence) of the human viruses. The majority of these avian substitutions were long-standing in the evolution of H7N9, and only 17 were first detected in 2013 as possibly essential for the initial human adaptation. Strikingly, continued evolution of the avian H7N9 virus has resulted in avian and human protein sequences that are almost identical. This rapid and continued adaptation of the avian H7N9 virus to the human host, with near identity of the avian and human viruses, is associated with increased human infection and a predicted greater risk of human-to-human transmission.

show abstract

“…For example, H3N2 viruses have continuously circulated in human population since the 1968 pandemic. Influenza A viruses contain eight gene segments, which include PB2, PB1, PA, HA, NP, NA, M, and NS [2]. Antigenic shift is caused by reassorting of gene segments while antigenic drift is caused by an accumulation of mutations in genes during virus evolution.…”

Section: Introductionmentioning

confidence: 99%

Genetic variations on 31 and 450 residues of influenza A nucleoprotein affect viral replication and translation

et al. 2020

View full text Add to dashboard Cite

Background: Influenza A viruses cause epidemics/severe pandemics that pose a great global health threat. Among eight viral RNA segments, the multiple functions of nucleoprotein (NP) play important roles in viral replication and transcription. Methods: To understand how NP contributes to the virus evolution, we analyzed the NP gene of H3N2 viruses in Taiwan and 14,220 NP sequences collected from Influenza Research Database. The identified genetic variations were further analyzed by mini-genome assay, virus growth assay, viral RNA and protein expression as well as ferret model to analyze their impacts on viral replication properties.Results: The NP genetic analysis by Taiwan and global sequences showed similar evolution pattern that the NP backbones changed through time accompanied with specific residue substitutions from 1999 to 2018. Other than the conserved residues, fifteen sporadic substitutions were observed in which the 31R, 377G and 450S showed higher frequency. We found 31R and 450S decreased polymerase activity while the dominant residues (31 K and 450G) had higher activity. The 31 K and 450G showed better viral translation and replication in vitro and in vivo.Conclusions: These findings indicated variations identified in evolution have roles in modulating viral replication in vitro and in vivo. This study demonstrates that the interaction between variations of NP during virus evolution deserves future attention.

show abstract

SnapShot: Evolution of Human Influenza A Viruses

Cited by 11 publications

References 0 publications

Balancing Immune Protection and Immune Pathology by CD8+ T-Cell Responses to Influenza Infection

Balancing Immune Protection and Immune Pathology by CD8+ T-Cell Responses to Influenza Infection

Avian Influenza H7N9 Virus Adaptation to Human Hosts

Genetic variations on 31 and 450 residues of influenza A nucleoprotein affect viral replication and translation

Contact Info

Product

Resources

About