Adaptation of Avian Influenza A Virus Polymerase in Mammals To Overcome the Host Species Barrier

Mänz, Benjamin; Schwemmle, Martin; Brunotte, Linda

doi:10.1128/jvi.00980-13

Cited by 198 publications

(197 citation statements)

References 158 publications

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“…Z puli przebadanych próbek jedynie 6 surowic (2,8%) reagowało w teście HI, w niskim mianie (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), ze szczepami ludzkimi ICV.…”

Section: Zakażenia Ludzi Idvunclassified

Prevalence of infections with a new type of influenza virus – influenza D virus in humans and animals

Markowska-Daniel¹,

Mickiewicz²,

Witkowski³

et al. 2016

Medycyna Weterynaryjna

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In April 2011, in the USA, a new influenza virus type D (IDV) was isolated for the first time from pigs and then from cows. In the paper the data about the prevalence of this virus in humans and animals are described. It was evidenced that HE protein of IDV could bind to cellular receptors in the epithelium of the human trachea. Moreover, the new virus was shown to infect and spread in ferrets. These findings make it possible to conclude that IDV seems to be able to infect humans and have zoonotic potential. Up to now the percent of human seroconverted to IDV has been low, about 1.3%. The susceptibility of pigs to IDV has been shown in natural and experimental conditions. Virus specific antibodies were detected in 9.5% of pigs. Additionally the isolates from pigs were obtained in the USA and Italy. This suggests that pigs are not the natural reservoir of this virus and the infections are uncommon in pig populations. Several studies demonstrated that the new virus is widely spread in cattle. It was isolated in the USA, Canada, China, France and Italy, which proved that the intercontinental transmission of IDV had occurred. The highest percentage of infected cows, mainly animals manifesting BRDC symptoms, was found in Minnesota, Oklahoma and Mississippi, and it varied from 4.8 to 29.1%. Additionally the virus was detected in 2.4% of healthy animals. Seroconversion was demonstrated in 32.7 to 87.5% of the bovine herds tested in Mississippi and Minnesota, respectively. Retrospective analysis revealed that antibodies specific to IDV had been detected in bovine samples since 2004. This suggests that the new virus has circulated in cattle at least since 2004. The analysis of the relationship between the seroconversion and the age of animals showed that over 50% of cows aged 1–14 years were seropositive. Also more than 90% of newborn calves had maternal antibodies to IDV. The spread of IDV was also linked to the type of farm, with the lowest percentage of animals seroconverting in closed herds and the highest in order-buying facilities. Therefore cattle seem to be the natural host of IDV. In the USA and Canada the infections caused by IDV were also found in sheep and goats. Herd-level and individual-level seroprevalence in sheep was 15.3 and 6.1%, respectively, and these figures were even higher in goats: 20% and 25.9%, respectively. This shows that small ruminants are susceptible to IDV infection. Moreover, retrospective analysis confirmed that one serum from a goat taken in Massachusetts in 2002 was positive to IDV. This suggests that the new virus may have circulated among goats as early as in 2002. Serological studies of chicken and turkey sera from the herds in Minnesota, located near the positive bovine herds, yielded negative results. This might suggest that birds are resistant to IDV infection; however, the number of birds tested is insufficient to substantiate such a statement. The studies aimed at evaluation of zoonotic potential of the new virus proved that it replicated efficiently in the upper respiratory tract of ferrets. This suggests that the new virus may have an influence on public health. In experimental conditions the susceptibility of guinea pigs to IDV infection was also evidenced. In conclusion, all the studies demonstrated that cattle were the natural reservoir of the new virus, despite the fact that humans as well as various animal species could also be infected. Furthermore, cattle are likely to be a potential source of infection for both animals and humans.

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“…Z puli przebadanych próbek jedynie 6 surowic (2,8%) reagowało w teście HI, w niskim mianie (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), ze szczepami ludzkimi ICV.…”

Section: Zakażenia Ludzi Idvunclassified

Prevalence of infections with a new type of influenza virus – influenza D virus in humans and animals

Markowska-Daniel¹,

Mickiewicz²,

Witkowski³

et al. 2016

Medycyna Weterynaryjna

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“…Wywołują one infekcje zarówno u ludzi, jak i u licznych gatunków ssaków, w tym u zwierząt gospodarskich (świnie, konie), zwierząt towarzyszących (psy, okazjonalnie koty), zwierząt egzotycznych (tygrysy, pantery, lamparty, gepardy, cywety, pandy, szopy), ssaków morskich (foki, wieloryby), wielbłądów, norek, fretek, nietoperzy oraz u wielu gatunków ptaków hodowlanych i dzikich (4,12,16,19,20,25). Naturalnym rezerwuarem IAV jest dzikie ptactwo wodne.…”

Section: Electron Microscopic Studies Demonstrated Features Characterunclassified

Characterization of a new influenza virus type D

Markowska-Daniel¹,

Mickiewicz²,

Witkowski³

et al. 2016

Medycyna Weterynaryjna

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Influenza is caused by viruses belonging to the Orthomyxoviridae family. Currently three types of influenza virus are known: A (Influenza A virus, IAV), B (IBV) and C (ICV). Despite the fact that all these viruses are derived from a common ancestor they differ from each other by the number of segments, the size and sequence of RNA segments, antigenicity, pathogenicity and the spectrum of natural reservoirs. In 2011, a new influenza virus was isolated in the USA from pigs manifesting influenza-like symptoms. The virus was the most closely related to ICV. It was able to replicate in vitro in different cell cultures and displayed much broader cell tropism than human ICV. Moreover, in contrast to ICV, it was able to replicate at 370C. Electron microscopic studies demonstrated features characteristic of Orthomyxoviruses. Despite morphological and organizational similarities, the biological properties of the new virus, including biochemical activity, differ from that of other influenza viruses. Enzymatic assays revealed that the new virus had negligible neuraminidase but detectable O-acetyloesterase activity. Further studies evidenced that the new virus varied from ICV in receptor binding, despite its sharing a conserved array of functional domains in the viral RNA genome replication and viral entry machinery. Analysis conducted with the use of the model of crystal structure of the hemagglutinin-esterase fusion protein (HE) of the new virus and its receptor demonstrated that this protein was multifunctional. It catalyzes cellular receptor binding, receptor cleavage, as well as membrane fusion. Moreover, divergent receptor-binding sites than HE of ICV have been discovered in the new virus. These amino acid differences may alter the binding specificity and affinity of the HE protein to the receptor that in turn result in the observed differences in cellular tropism between the two viruses. It also possesses an open channel between the 230-helix and 270-loop in the receptor-binding site, which is a unique feature of this virus. This might explain why the new virus has a broad cell tropism. It is possible that the sequence variation in the fusion domain may influence the replication of this virus at a higher temperature when compared to ICV. Next-generation sequencing demonstrated that the genome of the new virus, similarly to ICV, had seven single-stranded negative-sense RNA segments coding 9 viral proteins. Deep RNA sequencing found a M1 protein expression strategy different from that of ICV. Studies aimed at evaluating of the evolutionary relationship of both viruses revealed that the new virus and ICV shared an approximately 69-72% mean pairwise identity in the PB1 gene, which is reported to be the most conserved influenza virus protein. Additionally, differences were detected at 5’ and 3’ends of noncoding regions, which are also highly conserved. They both may be responsible for the lack of in vitro reassortment between ICV of human origin and the new virus. In the study characterizing antigenic properties of the new virus, no cross-reactivity was observed using HI and AGID tests. This indicates the major differences in conserved proteins M1 and NP between both viruses. Summing up, despite the fact that new virus is the most closely related to human ICV, the number of important antigenic and genetic distinctions among them is the basis for suggesting that the International Committee of Virus Taxonomy classify it as a separate genus - D. There is no doubt that the discovery of a new influenza virus genus will have a great impact on influenza research and ecology.

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“…Described substitutions in PB2 were shown to enhance the polymerase activity at lower temperature, but the exact mechanism is not yet clear. In PA and PB1 subunits were also found mutations that increased the avian IAV polymerase activity in mammalian cells (Mänz et al, 2013). Nowadays, the PB1-F2 protein, the product expressed from an alternative open reading frame within the PB1 gene, is considered to be also a viral factor of pathogenicity.…”

Section: Other Iav Proteins Infl Uencing the Virulencementioning

confidence: 99%

“…It was documented that avian IAV can cause zoonotic infections in humans. Most of these infections are so-called "dead-end", which means they are not further spread among the individuals of the new host (Mänz et al, 2013). Th e lack of avian IAV transmission in new host is the result of diff erences in their interaction with the new host, which require adaptation changes in IAV genome.…”

Section: Th E Role Of Fusion Activation Ph and Stability Of Ha In Thementioning

confidence: 99%

“…In spite of high conservation of these proteins, host-specifi c amino acid substitutions were identifi ed during the process of adaptation of avian viruses to the new host and are considered as host markers of IAV viruses. Th e adaptive changes were identifi ed in all three IAV polymerase subunits (PB2, PB1 and PA) as well as in NP (Mänz et al, 2013). Th e most frequently described adaptive mutations are E627K and D701N in PB2 protein (Subbarao et al, 1993;Salomon et al, 2006;Hatta et al, 2007;Kim et al, 2010;Gabriel and Fodor, 2014).…”

Section: Other Iav Proteins Infl Uencing the Virulencementioning

confidence: 99%

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The role of fusion activity of influenza A viruses in their biological properties

Jakubcová¹,

Hollý²,

Varečková³

2016

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Summary. -Infl uenza A viruses (IAVs) cause acute respiratory infections of humans, which are repeated yearly. Human IAV infections are associated with signifi cant morbidity and mortality and therefore they represent a serious health problem. All human IAV strains are originally derived from avian IAVs, which, aft er their adaptation to humans, can spread in the human population and cause pandemics with more or less severe course of the disease. Presently, however, the potential of avian IAV to infect humans and to cause the disease cannot be predicted. Many studies are therefore focused on factors infl uencing the virulence and pathogenicity of IAV viruses in a given host. Th e virus-host interaction starts by virus attachment via the envelope glycoprotein hemagglutinin (HA) to the receptors on the cell surface. In addition to receptor binding, HA mediates also the fusion of viral and endosomal membranes, which follows the virus endocytosis. Th e fusion potential of HA trimer, primed by proteolytic cleavage, is activated by low pH in endosomes, resulting in HA refolding into the fusion-active form. Th e HA conformation change is predetermined by its 3-D structure, is pH-dependent, irreversible and strain-specifi c. Th e process of fusion activation of IAV hemagglutinin is crucial for virus entry into the cell and for the ability of the virus to replicate in the host. Here we discuss the known data about the characteristics of fusion activation of HA in relation to IAV virulence and pathogenicity.Keywords: infl uenza A viruses; pH optimum of fusion; IAV virulence and pathogenicity; HA conformation change; IAV interspecies transmission; adaptation changes * Corresponding author. E-mail: viruevar@savba.sk; phone: 421-2-59302427. Abbreviations: HA = hemagglutinin; HA0 = HA precursor; HA1 = heavy chain of HA; HA2 = light chain of HA; HPAI = highly pathogenic avian infl uenza; IAV(s) = infl uenza A virus(es); LPAI = low pathogenic avian infl uenza; M1 protein = matrix protein; mRNA = messenger RNA; NA = neuraminidase; NEP protein = nuclear export protein; NS1 protein = nonstructural protein 1; PA = polymerase acidic protein; PB1 = polymerase basic protein 1; PB2 = polymerase basic protein 2; RBS = receptor binding site; RNA = ribonucleic acid; RNP = ribonucleoprotein; SA = sialic acid; vRNA = viral RNA Content: 1. Introduction 2. Structure and function of hemagglutinin 2.1 Receptor binding activity and IAV host tropism 2.2 Fusion activity and structural rearrangements of HA during the membrane fusion 3. Th e HA cleavability by host proteases and HA fusion activation pH as factors of IAV virulence and pathogenicity 3.1 Cleavage activation of HA as a determinant of IAV pathogenicity 3.2 Fusion activation pH as a determinant of IAV virulence 4. Th e role of fusion activation pH and stability of HA in the adaptation of IAV to the new host 5. Other viral proteins infl uencing the IAV virulence 6. Conclusion

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Adaptation of Avian Influenza A Virus Polymerase in Mammals To Overcome the Host Species Barrier

Cited by 198 publications

References 158 publications

Prevalence of infections with a new type of influenza virus – influenza D virus in humans and animals

Prevalence of infections with a new type of influenza virus – influenza D virus in humans and animals

Characterization of a new influenza virus type D

The role of fusion activity of influenza A viruses in their biological properties

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