Structure of Influenza Virus Neuraminidase B/Lee/40 Complexed with Sialic Acid and a Dehydro Analog at 1.8-.ANG. Resolution: Implications for the Catalytic Mechanism

Janakiraman, M.N.; White, C. L.; Laver, W.G.; Air, Gillian M.; Luo, Ming

doi:10.1021/bi00193a002

Cited by 100 publications

(83 citation statements)

References 11 publications

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“…Although seal11 NA has four potential N-linked glycosylation sites at Asn84, Asn144, Asn293, and Asn398 (residues 86, 146, 294, and 402 in N2 numbering), our expression construct included an Asn84Gln substitution that removed one of these sites. For the remaining three sites, the final model had interpretable glycan density at only one site, Asn144 (residue 146 in N2 numbering), which is situated on the membrane-distal surface close to the active site and is the only glycosylation site conserved among all other influenza A and B NAs (72,74,80). Active site of seal11 NA and antiviral drug susceptibility with oseltamivir and zanamivir.…”

Section: Resultsmentioning

confidence: 99%

Structural and Functional Analysis of Surface Proteins from an A(H3N8) Influenza Virus Isolated from New England Harbor Seals

Yang

Nguyen

Carney

et al. 2015

J Virol

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In late 2011, an A(H3N8) influenza virus infection resulted in the deaths IMPORTANCECross-species transmission of zoonotic influenza viruses increases public health concerns. Here, we report a molecular and structural study of the major surface proteins from an A(H3N8) influenza virus isolated from New England harbor seals. The results improve our understanding of these viruses as they evolve and provide important information to aid ongoing risk assessment analyses as these zoonotic influenza viruses continue to circulate and adapt to new hosts. Influenza A viruses (IAVs) are classified into subtypes according to the serological reactivity of their surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA) (1, 2). While 16 HA (H1 to H16) and 9 NA (N1 to N9) subtypes have been identified in wild aquatic birds in the last 100 years, only 3 have adapted to the human population, resulting in four pandemics: H1N1 in 1918 and 2009, H2N2 in 1957, and H3N2 in 1968 (3-6). Although aquatic birds are believed to be the natural reservoir for influenza viruses (7), two novel subtypes of influenza A viruses, H17N10 and H18N11, were recently described in New World bats, which thus may be an alternate reservoir of influenza viruses in nature (8,9).Since the first isolation of H1N1 IAV in swine (10) and the subsequent observation that ferrets were susceptible to IAV (11), it became evident that multiple IAV subtypes of either avian or human descent can infect a number of mammalian species (1). Indeed, over the last decade, the perception and impact of influenza virus infections in animals have changed dramatically as a result of a number of recent outbreaks in poultry involving viruses from the H5, H7, and H9 subtypes that resulted in Ͼ1,000 human infections, as well as the swine origin of the recent A(H1N1)pdm09 pandemic virus (4,(12)(13)(14). This has prompted some governments to invest heavily in global surveillance, research, and capacity building. Public health officials now have a keen interest in all IAVs, but particularly in whether animals, such as pigs, that are closely associated with humans can represent a possible pathway for increased interspecies virus adaptation and transmission.Similar to the infection of pigs, IAV (i.e., H7N7, H4N5, H3N3, H13N2, H13N9, and H4N6 subtypes) and influenza B virus infections have been detected in marine mammals, including seals, whales, and sea otters (15)(16)(17)(18)(19)(20)(21)(22). In November 2011, a marine mammal "unusual mortality event" was declared for Maine, New Hampshire, and northern Massachusetts in response to a large number of deaths in the New England harbor seal population. Sequence analysis revealed that an avian-like H3N8 influenza A virus, A/harbor seal/Massachusetts/1/2011 (seal11), was the cause of the outbreak (23). Although A(H3N8), usually found in avian, canine, equine, and swine hosts (24-27), had been isolated from a seal prior to this event (28), the high mortality observed increased interest from public health officials.Here, we focus our...

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Section: Resultsmentioning

confidence: 99%

Structural and Functional Analysis of Surface Proteins from an A(H3N8) Influenza Virus Isolated from New England Harbor Seals

Yang

Nguyen

Carney

et al. 2015

J Virol

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“…The pyranose ring of the sialic acid assumes the usual chair conformation with all constituent groups at equatorial positions except for the characteristic carboxylate. In several cases, the negatively charged carboxyl group of sialic acid interacts with positively charged side chains when binding to proteins (16,27,41). In the DA virus, however, a hydrogen bond between the carboxylate and the side chain of VP2 Gln2161 was found (Fig.…”

Section: Resultsmentioning

confidence: 99%

Sialylation of the Host Receptor May Modulate Entry of Demyelinating Persistent Theiler's Virus

Zhou

Luo

Wu³

et al. 2000

J Virol

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Theiler's murine encephalomyelitis virus (TMEV) is a picornavirus of the Cardiovirus genus. Certain strains of TMEV may cause a chronic demyelinating disease, which is very similar to multiple sclerosis in humans, associated with a persistent viral infection in the mouse central nervous system (CNS). Other strains of TMEV only cause an acute infection without persistence in the CNS. It has been shown that sialic acid is a receptor moiety only for the persistent TMEV strains and not for the nonpersistent strains. We report the effect of sialylation on cell surface on entry and the complex structure of DA virus, a persistent TMEV, and the receptor moiety mimic, sialyllactose, refined to a resolution of 3.0 Å. The ligand binds to a pocket on the viral surface, composed mainly of the amino acid residues from capsid protein VP2 puff B, in the vicinity of the VP1 loop and VP3 C terminus. The interaction of the receptor moiety with the persistent DA strain provides new understanding for the demyelinating persistent infection in the mouse CNS by TMEV.Theiler's murine encephalomyelitis virus (TMEV) belongs to the Cardiovirus genus of the family Picornaviridae based on sequence analysis (34). Based on the characteristics of the disease they cause, TMEV strains are divided into two groups. Viruses of one group, including strain GDVII and FA, are highly neurovirulent, causing a rapid destruction of the neuron and killing their host in a matter of days. These viruses are unable to persist and to induce demyelination in those rare survivors (22). The other group, including strains DA, BeAn, WW, TO4, and Yale, are referred to as the Theiler's original (TO) group (23). Viruses of the TO group are much less virulent than GDVII and FA and cause a biphasic disease with mild central nervous system (CNS) damage. The first phase, or early onset, is acute encephalitis that occurs during the initial few days following intracranial inoculation. At that time, the virus is also found in neurons of the gray matter in the brain and spinal cord. However, the number of infected cells is small and most of the animals survive. Soon after, the neurons are cleared of the virus and the disease enters a second phase, or late onset, during which the virus is found to be persistent in the white matter of the spinal cord. At this stage of the viral persistence, patchy inflammation and demyelination develops in the spinal cord at the sites of infection (7, 23). The symptoms of the demyelination disease of mice caused by TMEV persistence infection in the CNS resemble those of multiple sclerosis (MS), a chronic demyelinating disease of the human CNS. Among the animal models of virus-induced demyelination in the last two decades, TMEV infection has emerged as one of the best models for studying MS.Although these two groups of TMEV strains have both been shown to replicate well in BHK-21 cells and share high amino acid sequence homology (31, 34-36), they apparently display different pathogenesis characteristics in vivo. Many efforts have been taken to map ...

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“…Under a variety of soaking conditions, sialic acid was seen bound in both the active site and the HB site of all four monomers. In the active site the sialic acid is in the twisted boat conformation that may result from its tight binding preceding catalysis 22,63,64 , while the sialic acid in the HB site is in the chair conformation as in N9 NB site and in HA 32,59 . Interestingly, although sialic acid in solution exists 95% as the β anomer, only the α configuration is seen in the HB binding site (Figure 3), which may explain the difficulty in locating the second sialic acid in N9 NA and the high concentration of sialic acid needed before the sialic acid is clearly seen.…”

Section: Some Nas Have a Second Sialic Acid Binding Sitementioning

confidence: 99%

Influenza neuraminidase

Air

2011

Influenza Resp Viruses

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215

216

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Influenza neuraminidase is the target of two licensed antivirals that have been very successful, with several more in development. However, neuraminidase has been largely ignored as a vaccine target despite evidence that inclusion of neuraminidase in the subunit vaccine gives increased protection. This article describes current knowledge on the structure, enzyme activity and antigenic significance of neuraminidase.

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Structure of Influenza Virus Neuraminidase B/Lee/40 Complexed with Sialic Acid and a Dehydro Analog at 1.8-.ANG. Resolution: Implications for the Catalytic Mechanism

Cited by 100 publications

References 11 publications

Structural and Functional Analysis of Surface Proteins from an A(H3N8) Influenza Virus Isolated from New England Harbor Seals

Structural and Functional Analysis of Surface Proteins from an A(H3N8) Influenza Virus Isolated from New England Harbor Seals

Sialylation of the Host Receptor May Modulate Entry of Demyelinating Persistent Theiler's Virus

Influenza neuraminidase

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