Amino acids adjacent to the haemagglutinin cleavage site are relevant for virulence of avian influenza viruses of subtype H5

Gohrbandt, Sandra; Veits, Jutta; Hundt, Jana; Bogs, Jessica; Breithaupt, Angele; Teifke, Jens Peter; Weber, Siegfried; Mettenleiter, Thomas C.; Stech, Jürgen

doi:10.1099/vir.0.023887-0

Cited by 41 publications

(41 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…*, the titer of SD16-316S/⌬NA was significantly higher than for SD16-WT virus (P Ͻ 0.05, ANOVA). site play important roles in recognition and binding of the protease, as well as for tissue tropism and pathogenicity in the host (12)(13)(14). Horimoto et al (15) proposed that the cleavability level of HA correlates with the degree of virulence when all other genetic characteristics are considered equal.…”

Section: Fig 3 In Vitro Phenotype Of Wt and Mutant H9n2 Influenza Virmentioning

confidence: 99%

Amino Acid 316 of Hemagglutinin and the Neuraminidase Stalk Length Influence Virulence of H9N2 Influenza Virus in Chickens and Mice

Sun

Tan

Wei

et al. 2013

J Virol

View full text Add to dashboard Cite

e H9N2 influenza viruses with an A316S substitution in hemagglutinin (HA) and a shorter neuraminidase (NA) stalk have become predominant in China. The A316S was shown to increase HA cleavage efficiency when combined with short stalk NA, and the short stalk NA improved NA enzyme activity and release of virus from erythrocytes. Single mutations or combinations of these mutations strengthened the virulence of H9N2 virus in chickens and mice.

show abstract

Section: Fig 3 In Vitro Phenotype Of Wt and Mutant H9n2 Influenza Virmentioning

confidence: 99%

Amino Acid 316 of Hemagglutinin and the Neuraminidase Stalk Length Influence Virulence of H9N2 Influenza Virus in Chickens and Mice

Sun

Tan

Wei

et al. 2013

J Virol

View full text Add to dashboard Cite

show abstract

“…All plates were incubated at 37 C/5% CO 2 for 3 d and then fixed with formaldehyde (10%) containing crystal violet (0.1%). 38 Plaques were counted and plaque sizes were measured by using Nikon NIS-Elements software.…”

Section: Plaque Assaymentioning

confidence: 99%

Prevalence of the C-terminal truncations of NS1 in avian influenza A viruses and effect on virulence and replication of a highly pathogenic H7N1 virus in chickens

et al. 2016

View full text Add to dashboard Cite

(2016) Prevalence of the C-terminal truncations of NS1 in avian influenza A viruses and effect on virulence and replication of a highly pathogenic H7N1 virus in chickens, Virulence, 7:5, 546-557, DOI: 10.1080/21505594.2016 protein sequences of all AIV subtypes in birds from 1902 to 2015 were analyzed to study the prevalence and distribution of CTE truncation (DCTE). Thirteen different DCTE forms were observed in NS1 proteins from 11 HA and 8 NA subtypes with high prevalences in H9, H7, H6 and H10 and N9, N2, N6 and N1 subtypes particularly in chickens and minor poultry species. With 88% NS217 lacking amino acids 218-230 was the most common DCTE form followed by NS224 (3.6%). NS217 was found in 10 and 8 different HA and NA subtypes, respectively, whereas NS224 was detected exclusively in the Italian HPAIV H7N1 suggesting relevance for virulence. To test this assumption, 3 recombinant HPAIV H7N1 were constructed carrying wild-type HP NS1 (Hp-NS224), NS1 with extended CTE (Hp-NS230) or NS1 from LPAIV H7N1 (Hp-NSLp), and tested in-vitro and in-vivo. Extension of CTE in Hp NS1 significantly decreased virus replication in chicken embryo kidney cells. Truncation in the NS1 decreased the tropism of Hp-NS224 to the endothelium, central nervous system and respiratory tract epithelium without significant difference in virulence in chickens. This study described the variable forms of DCTE in NS1 and indicated that CTE is not an essential virulence determinant particularly for the Italian HPAIV H7N1 but may be a host-adaptation marker required for efficient virus replication.

show abstract

“…Unlike all other influenza A virus strains, HPAIVs have acquired a polybasic HA cleavage site (HACS) (5), which allows proteolytic HA activation by the ubiquitous protease furin (6). This polybasic HACS is considered the prime virulence determinant of HPAIV (7,8). Consequently, infection of gallinaceous poultry with HPAIV leads to systemic viral spread resulting in lethal disease.…”

mentioning

confidence: 99%

Avian influenza virus hemagglutinins H2, H4, H8, and H14 support a highly pathogenic phenotype

Veits

Weber²,

Stech³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

115

View full text Add to dashboard Cite

High-pathogenic avian influenza viruses (HPAIVs) evolve from lowpathogenic precursors specifying the HA serotypes H5 or H7 by acquisition of a polybasic HA cleavage site. As the reason for this serotype restriction has remained unclear, we aimed to distinguish between compatibility of a polybasic cleavage site with H5/H7 HA only and unique predisposition of these two serotypes for insertion mutations. To this end, we introduced a polybasic cleavage site into the HA of several low-pathogenic avian strains with serotypes H1, H2, H3, H4, H6, H8, H10, H11, H14, or H15, and rescued HA reassortants after cotransfection with the genes from either a low-pathogenic H9N2 or high-pathogenic H5N1 strain. Oculonasal inoculation with those reassortants resulted in varying pathogenicity in chicken. Recombinants containing the engineered H2, H4, H8, or H14 in the HPAIV background were lethal and exhibited i.v. pathogenicity indices of 2.79, 2.37, 2.85, and 2.61, respectively, equivalent to naturally occurring H5 or H7 HPAIV. Moreover, the H2, H4, and H8 reassortants were transmitted to some contact chickens. The H2 reassortant gained two mutations in the M2 proton channel gate region, which is affected in some HPAIVs of various origins. Taken together, in the presence of a polybasic HA cleavage site, non-H5/H7 HA can support a highly pathogenic phenotype in the appropriate viral background, indicating requirement for further adaptation. Therefore, the restriction of natural HPAIV to serotypes H5 and H7 is likely a result of their unique predisposition for acquisition of a polybasic HA cleavage site.

show abstract

Amino acids adjacent to the haemagglutinin cleavage site are relevant for virulence of avian influenza viruses of subtype H5

Cited by 41 publications

References 44 publications

Amino Acid 316 of Hemagglutinin and the Neuraminidase Stalk Length Influence Virulence of H9N2 Influenza Virus in Chickens and Mice

Amino Acid 316 of Hemagglutinin and the Neuraminidase Stalk Length Influence Virulence of H9N2 Influenza Virus in Chickens and Mice

Prevalence of the C-terminal truncations of NS1 in avian influenza A viruses and effect on virulence and replication of a highly pathogenic H7N1 virus in chickens

Avian influenza virus hemagglutinins H2, H4, H8, and H14 support a highly pathogenic phenotype

Contact Info

Product

Resources

About