Influenza virus proteins as factors involved in interspecies transmission

2014 ◽  
Vol 17 (4) ◽  
Author(s):  
I.M. Góra ◽  
W. Rożek ◽  
J.F. Żmudziński

AbstractInfluenza A viruses cause recurrent epidemics and global pandemics. One of the unique features of influenza virus is the ability to overcome interspecies barrier. Reassortment of viral genes and the accumulation of mutations contribute to the emergence of new influenza virus variants. The replication of influenza A virus in a specific host depends on many factors e.g. activity of viral proteins, host response system and environmental conditions. In this review the role of viral proteins as a condition for crossing the species barriers is discussed.

2010 ◽  
Vol 11 (1) ◽  
pp. 53-72 ◽  
Author(s):  
Hadi M. Yassine ◽  
Chang-Won Lee ◽  
Renukaradhya Gourapura ◽  
Yehia M. Saif

AbstractInfluenza A viruses are enveloped viruses belonging to the familyOrthomyxoviridaethat encompasses four more genera: Influenza B, Influenza C, Isavirus and Thogotovirus. Type A viruses belong to the only genus that is highly infectious to a variety of mammalian and avian species. They are divided into subtypes based on two surface glycoproteins, the hemagglutinin (HA) and neuraminidase (NA). So far, 16 HA and 9 NA subtypes have been identified worldwide, making a possible combination of 144 subtypes between both proteins. Generally, individual viruses are host-specific, however, interspecies transmission of influenza A viruses is not uncommon. All of the HA and NA subtypes have been isolated from wild birds; however, infections in humans and other mammalian species are limited to a few subtypes. The replication of individual influenza A virus in a specific host is dependent on many factors including, viral proteins, host system and environmental conditions. In this review, the key findings that contribute to the transmission of influenza A viruses amongst different species are summarized.


2017 ◽  
Vol 91 (7) ◽  
Author(s):  
Benjamin E. Nilsson ◽  
Aartjan J. W. te Velthuis ◽  
Ervin Fodor

ABSTRACT The RNA genome of influenza A viruses is transcribed and replicated by the viral RNA-dependent RNA polymerase, composed of the subunits PA, PB1, and PB2. High-resolution structural data revealed that the polymerase assembles into a central polymerase core and several auxiliary highly flexible, protruding domains. The auxiliary PB2 cap-binding and the PA endonuclease domains are both involved in cap snatching, but the role of the auxiliary PB2 627 domain, implicated in host range restriction of influenza A viruses, is still poorly understood. In this study, we used structure-guided truncations of the PB2 subunit to show that a PB2 subunit lacking the 627 domain accumulates in the cell nucleus and assembles into a heterotrimeric polymerase with PB1 and PA. Furthermore, we showed that a recombinant viral polymerase lacking the PB2 627 domain is able to carry out cap snatching, cap-dependent transcription initiation, and cap-independent ApG dinucleotide extension in vitro, indicating that the PB2 627 domain of the influenza virus RNA polymerase is not involved in core catalytic functions of the polymerase. However, in a cellular context, the 627 domain is essential for both transcription and replication. In particular, we showed that the PB2 627 domain is essential for the accumulation of the cRNA replicative intermediate in infected cells. Together, these results further our understanding of the role of the PB2 627 domain in transcription and replication of the influenza virus RNA genome. IMPORTANCE Influenza A viruses are a major global health threat, not only causing disease in both humans and birds but also placing significant strains on economies worldwide. Avian influenza A virus polymerases typically do not function efficiently in mammalian hosts and require adaptive mutations to restore polymerase activity. These adaptations include mutations in the 627 domain of the PB2 subunit of the viral polymerase, but it still remains to be established how these mutations enable host adaptation on a molecular level. In this report, we characterize the role of the 627 domain in polymerase function and offer insights into the replication mechanism of influenza A viruses.


2003 ◽  
Vol 77 (5) ◽  
pp. 3148-3156 ◽  
Author(s):  
Daniel R. Perez ◽  
Wilina Lim ◽  
Jon P. Seiler ◽  
Guan Yi ◽  
Malik Peiris ◽  
...  

ABSTRACT H9 influenza viruses have become endemic in land-based domestic poultry in Asia and have sporadically crossed to pigs and humans. To understand the molecular determinants of their adaptation to land-based birds, we tested the replication and transmission of several 1970s duck H9 viruses in chickens and quail. Quail were more susceptible than chickens to these viruses, and generation of recombinant H9 viruses by reverse genetics showed that changes in the HA gene are sufficient to initiate efficient replication and transmission in quail. Seven amino acid positions on the HA molecule corresponded to adaptation to land-based birds. In quail H9 viruses, the pattern of amino acids at these seven positions is intermediate between those of duck and chicken viruses; this fact may explain the susceptibility of quail to duck H9 viruses. Our findings suggest that quail provide an environment in which the adaptation of influenza viruses from ducks generates novel variants that can cross the species barrier.


2015 ◽  
Vol 89 (12) ◽  
pp. 6218-6226 ◽  
Author(s):  
Martha I. Nelson ◽  
Jered Stratton ◽  
Mary Lea Killian ◽  
Alicia Janas-Martindale ◽  
Amy L. Vincent

ABSTRACTThe diversity of influenza A viruses in swine (swIAVs) presents an important pandemic threat. Knowledge of the human-swine interface is particularly important for understanding how viruses with pandemic potential evolve in swine hosts. Through phylogenetic analysis of contemporary swIAVs in the United States, we demonstrate that human-to-swine transmission of pandemic H1N1 (pH1N1) viruses has occurred continuously in the years following the 2009 H1N1 pandemic and has been an important contributor to the genetic diversity of U.S. swIAVs. Although pandemic H1 and N1 segments had been largely removed from the U.S. swine population by 2013 via reassortment with other swIAVs, these antigens reemerged following multiple human-to-swine transmission events during the 2013-2014 seasonal epidemic. These findings indicate that the six internal gene segments from pH1N1 viruses are likely to be sustained long term in the U.S. swine population, with periodic reemergence of pandemic hemagglutinin (HA) and neuraminidase (NA) segments in association with seasonal pH1N1 epidemics in humans. Vaccinating U.S. swine workers may reduce infection of both humans and swine and in turn limit the role of humans as sources of influenza virus diversity in pigs.IMPORTANCESwine are important hosts in the evolution of influenza A viruses with pandemic potential. Here, we analyze influenza virus sequence data generated by the U.S. Department of Agriculture's national surveillance system to identify the central role of humans in the reemergence of pandemic H1N1 (pH1N1) influenza viruses in U.S. swine herds in 2014. These findings emphasize the important role of humans as continuous sources of influenza virus diversity in swine and indicate that influenza viruses with pandemic HA and NA segments are likely to continue to reemerge in U.S. swine in association with seasonal pH1N1 epidemics in humans.


2019 ◽  
Vol 32 (1) ◽  
pp. 15-20
Author(s):  
Oliver Gittins ◽  
Llorenç Grau-Roma ◽  
Rosa Valle ◽  
Francesc Xavier Abad ◽  
Miquel Nofrarías ◽  
...  

AbstractTo evaluate how avian influenza virus (AIV) circulates among the avifauna of the Antarctic and sub-Antarctic islands, we surveyed 14 species of birds from Marion, Livingston and Gough islands. A competitive enzyme-linked immunosorbent assay was carried out on the sera of 147 birds. Quantitative reverse transcription polymerase chain reaction was used to detect the AIV genome from 113 oropharyngeal and 122 cloacal swabs from these birds. The overall seroprevalence to AIV infection was 4.8%, with the only positive results coming from brown skuas (Catharacta antarctica) (4 out of 18, 22%) and southern giant petrels (Macronectes giganteus) (3 out of 24, 13%). Avian influenza virus antibodies were detected in birds sampled from Marion and Gough islands, with a higher seroprevalence on Marion Island (P = 0.014) and a risk ratio of 11.29 (95% confidence interval: 1.40–91.28) compared to Gough Island. The AIV genome was not detected in any of the birds sampled. These results confirm that AIV strains are uncommon among Antarctic and sub-Antarctic predatory seabirds, but they may suggest that scavenging seabirds are the main avian reservoirs and spreaders of this virus in the Southern Ocean. Further studies are necessary to determine the precise role of these species in the epidemiology of AIV.


Viruses ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 171 ◽  
Author(s):  
Robert Meineke ◽  
Guus Rimmelzwaan ◽  
Husni Elbahesh

Influenza A viruses (IAVs) are a major cause of respiratory illness and are responsible for yearly epidemics associated with more than 500,000 annual deaths globally. Novel IAVs may cause pandemic outbreaks and zoonotic infections with, for example, highly pathogenic avian influenza virus (HPAIV) of the H5N1 and H7N9 subtypes, which pose a threat to public health. Treatment options are limited and emergence of strains resistant to antiviral drugs jeopardize this even further. Like all viruses, IAVs depend on host factors for every step of the virus replication cycle. Host kinases link multiple signaling pathways in respond to a myriad of stimuli, including viral infections. Their regulation of multiple response networks has justified actively targeting cellular kinases for anti-cancer therapies and immune modulators for decades. There is a growing volume of research highlighting the significant role of cellular kinases in regulating IAV infections. Their functional role is illustrated by the required phosphorylation of several IAV proteins necessary for replication and/or evasion/suppression of the innate immune response. Identified in the majority of host factor screens, functional studies further support the important role of kinases and their potential as host restriction factors. PKC, ERK, PI3K and FAK, to name a few, are kinases that regulate viral entry and replication. Additionally, kinases such as IKK, JNK and p38 MAPK are essential in mediating viral sensor signaling cascades that regulate expression of antiviral chemokines and cytokines. The feasibility of targeting kinases is steadily moving from bench to clinic and already-approved cancer drugs could potentially be repurposed for treatments of severe IAV infections. In this review, we will focus on the contribution of cellular kinases to IAV infections and their value as potential therapeutic targets.


Viruses ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 736 ◽  
Author(s):  
Rebekah E. Dumm ◽  
Nicholas S. Heaton

Influenza B viruses (IBVs) are major contributors to total human influenza disease, responsible for ~1/3 of all infections. These viruses, however, are relatively less studied than the related influenza A viruses (IAVs). While it has historically been assumed that the viral biology and mechanisms of pathogenesis for all influenza viruses were highly similar, studies have shown that IBVs possess unique characteristics. Relative to IAV, IBV encodes distinct viral proteins, displays a different mutational rate, has unique patterns of tropism, and elicits different immune responses. More work is therefore required to define the mechanisms of IBV pathogenesis. One valuable approach to characterize mechanisms of microbial disease is the use of genetically modified pathogens that harbor exogenous reporter genes. Over the last few years, IBV reporter viruses have been developed and used to provide new insights into the host response to infection, viral spread, and the testing of antiviral therapeutics. In this review, we will highlight the history and study of IBVs with particular emphasis on the use of genetically modified viruses and discuss some remaining gaps in knowledge that can be addressed using reporter expressing IBVs.


2008 ◽  
Vol 82 (10) ◽  
pp. 4834-4843 ◽  
Author(s):  
I-Chueh Huang ◽  
Wenhui Li ◽  
Jianhua Sui ◽  
Wayne Marasco ◽  
Hyeryun Choe ◽  
...  

ABSTRACT Enveloped viruses use multiple mechanisms to inhibit infection of a target cell by more than one virion. These mechanisms may be of particular importance for the evolution of segmented viruses, because superinfection exclusion may limit the frequency of reassortment of viral genes. Here, we show that cellular expression of influenza A virus neuraminidase (NA), but not hemagglutinin (HA) or the M2 proton pump, inhibits entry of HA-pseudotyped retroviruses. Cells infected with H1N1 or H3N2 influenza A virus were similarly refractory to HA-mediated infection and to superinfection with a second influenza A virus. Both HA-mediated entry and viral superinfection were rescued by the neuraminidase inhibitors oseltamivir carboxylate and zanamivir. These inhibitors also prevented the removal of α-2,3- and α-2,6-linked sialic acid observed in cells expressing NA or infected with influenza A viruses. Our data indicate that NA alone among viral proteins limits influenza A virus superinfection.


Vaccines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 40
Author(s):  
Wen-Chun Liu ◽  
Raffael Nachbagauer ◽  
Daniel Stadlbauer ◽  
Shirin Strohmeier ◽  
Alicia Solórzano ◽  
...  

Epidemic or pandemic influenza can annually cause significant morbidity and mortality in humans. We developed novel chimeric hemagglutinin (cHA)-based universal influenza virus vaccines, which contain a conserved HA stalk domain from a 2009 pandemic H1N1 (pH1N1) strain combined with globular head domains from avian influenza A viruses. Our previous reports demonstrated that prime-boost sequential immunizations induced robust antibody responses directed toward the conserved HA stalk domain in ferrets. Herein, we further followed vaccinated animals for one year to compare the efficacy and durability of these vaccines in the preclinical ferret model of influenza. Although all cHA-based immunization regimens induced durable HA stalk-specific and heterosubtypic antibody responses in ferrets, sequential immunization with live-attenuated influenza virus vaccines (LAIV-LAIV) conferred the best protection against upper respiratory tract infection by a pH1N1 influenza A virus. The findings from this study suggest that our sequential immunization strategy for a cHA-based universal influenza virus vaccine provides durable protective humoral and cellular immunity against influenza virus infection.


2018 ◽  
Vol 3 (2) ◽  
pp. 1-2
Author(s):  
Bishnu Prasad Upadhyay

Influenza virus type A and B are responsible for seasonal epidemics as well as pandemics in human. Influenza A viruses are further divided into two major groups namely, low pathogenic seasonal influenza (A/H1N1, A/H1N1 pdm09, A/H3N2) and highly pathogenic influenza virus (H5N1, H5N6, H7N9) on the basis of two surface antigens: hemagglutinin (HA) and neuraminidase (NA). Mutations, including substitutions, deletions, and insertions, are one of the most important mechanisms for producing new variant of influenza viruses. During the last 30 years; more than 50 viral threat has been evolved in South-East Asian countriesof them influenza is one of the major emerging and re-emerging infectious diseases of global concern. Similar to tropical and sub-tropical countries of Southeast Asia; circulation of A/H1N1 pdm09, A/H3N2 and influenza B has been circulating throughout the year with the peak during July-November in Nepal. However; the rate of infection transmission reach peak during the post-rain and winter season of Nepal.


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