Residue 41 of the Eurasian Avian-Like Swine Influenza A Virus Matrix Protein Modulates Virion Filament Length and Efficiency of Contact Transmission

Campbell, Patricia; Kyriakis, Constantinos S.; Marshall, Nicolle; Suppiah, Suganthi; Seladi-Schulman, Jill; Danzy, Shamika; Steel, John

doi:10.1128/jvi.00119-14

Cited by 33 publications

(28 citation statements)

References 44 publications

(59 reference statements)

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“…The matrix protein forms an inner core of the virion, giving structure and shape to an otherwise pleiomorphic lipid bilayer envelope [ 82 ]. The virus particles can adopt a range of morphologies ranging from rather spherical forms to extended filamentous structures, dictated at least in part by residues in the M1 protein [ 82 , 83 , 84 , 85 , 86 , 87 , 88 ]. Typically, spherical strains are found by electron microscopy in lab-adapted cultures, usually 80–100 nM in diameter, while most natural isolates are filamentous and vary in length [ 84 , 89 , 90 ].…”

Section: Influenza Virus and Host Receptor Interactionsmentioning

confidence: 99%

The Interplay between the Host Receptor and Influenza Virus Hemagglutinin and Neuraminidase

Byrd-Leotis

Cummings

Steinhauer

2017

IJMS

170

140

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The hemagglutinin (HA) and neuraminidase (NA) glycoproteins of influenza A virus are responsible for the surface interactions of the virion with the host. Entry of the virus is mediated by functions of the HA: binding to cellular receptors and facilitating fusion of the virion membrane with the endosomal membrane. The HA structure contains receptor binding sites in the globular membrane distal head domains of the trimer, and the fusion machinery resides in the stem region. These sites have specific characteristics associated with subtype and host, and the differences often define species barriers. For example, avian viruses preferentially recognize α2,3-Sialic acid terminating glycans as receptors and mammalian viruses recognize α2,6-Sialic acid. The neuraminidase, or the receptor-destroying protein, cleaves the sialic acid from cellular membrane constituents and viral glycoproteins allowing for egress of nascent virions. A functional balance of activity has been demonstrated between the two glycoproteins, resulting in an optimum level of HA affinity and NA enzymatic cleavage to allow for productive infection. As more is understood about both HA and NA, the relevance for functional balance between HA and NA continues to expand, with potential implications for interspecies transmission, host adaptation, and pathogenicity.

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Section: Influenza Virus and Host Receptor Interactionsmentioning

confidence: 99%

The Interplay between the Host Receptor and Influenza Virus Hemagglutinin and Neuraminidase

Byrd-Leotis

Cummings

Steinhauer

2017

IJMS

170

140

View full text Add to dashboard Cite

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“…Previous studies have shown that airborne H7N9 virus transmission can occur, albeit with low efficiency in ferrets 11 12 13 14 , the standard model used to simulate transmissibility among humans 15 . Several viral factors can contribute to the adaptability of avian-like viruses to mammals 16 : virus morphology 17 , receptor-binding specificity 18 , changes in glycosylation patterns of the hemagglutinin (HA) 19 , polymerase activity 20 , the acid stability of the HA 21 and the HA-neuraminidase (NA) balance 22 . Variation in these traits may be controlled by only a few amino-acid substitutions in a virus genome 17 20 21 22 .…”

mentioning

confidence: 99%

“…Several viral factors can contribute to the adaptability of avian-like viruses to mammals 16 : virus morphology 17 , receptor-binding specificity 18 , changes in glycosylation patterns of the hemagglutinin (HA) 19 , polymerase activity 20 , the acid stability of the HA 21 and the HA-neuraminidase (NA) balance 22 . Variation in these traits may be controlled by only a few amino-acid substitutions in a virus genome 17 20 21 22 . Only a few amino-acid changes are required to allow an avian-adapted virus to become airborne-transmissible between mammals, as was demonstrated in the influenza A(H5N1) viruses 23 24 .…”

mentioning

confidence: 99%

Mammalian adaptation of influenza A(H7N9) virus is limited by a narrow genetic bottleneck

et al. 2015

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Human infection with avian influenza A(H7N9) virus is associated mainly with the exposure to infected poultry. The factors that allow interspecies transmission but limit human-to-human transmission are unknown. Here we show that A/Anhui/1/2013(H7N9) influenza virus infection of chickens (natural hosts) is asymptomatic and that it generates a high genetic diversity. In contrast, diversity is tightly restricted in infected ferrets, limiting further adaptation to a fully transmissible form. Airborne transmission in ferrets is accompanied by the mutations in PB1, NP and NA genes that reduce viral polymerase and neuraminidase activity. Therefore, while A(H7N9) virus can infect mammals, further adaptation appears to incur a fitness cost. Our results reveal that a tight genetic bottleneck during avian-to-mammalian transmission is a limiting factor in A(H7N9) influenza virus adaptation to mammals. This previously unrecognized biological mechanism limiting species jumps provides a measure of adaptive potential and may serve as a risk assessment tool for pandemic preparedness.

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“…Mutations in the viral matrix protein of swine influenza A virus have been shown to induce changes in virus shape (39) and to increase virulence in mice (40). Thus, we suggested that the D184N mutation influences the shape of MARV particles and/or the incorporation of the surface glycoprotein GP and explains the increased infectivity of rMARV VP40(D184N) in guinea pig cells compared to that of rMARV WT -infected cells.…”

Section: Discussionmentioning

confidence: 89%

A Single Amino Acid Change in the Marburg Virus Matrix Protein VP40 Provides a Replicative Advantage in a Species-Specific Manner

Koehler

Kolesnikova

Welzel

et al. 2016

J Virol

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Marburg virus (MARV) induces severe hemorrhagic fever in humans and nonhuman primates but only transient nonlethal disease in rodents. However, sequential passages of MARV in rodents boosts infection leading to lethal disease. Guinea pig-adapted MARV contains one mutation in the viral matrix protein VP40 at position 184 (VP40 D184N ). The contribution of the D184N mutation to the efficacy of replication in a new host is unknown. In the present study, we demonstrated that recombinant MARV containing the D184N mutation in VP40 [rMARV VP40(D184N) ] grew to higher titers than wild-type recombinant MARV (rMARV WT ) in guinea pig cells. Moreover, rMARV VP40(D184N) displayed higher infectivity in guinea pig cells. Comparative analysis of VP40 functions indicated that neither the interferon (IFN)-antagonistic function nor the membrane binding capabilities of VP40 were affected by the D184N mutation. However, the production of VP40-induced virus-like particles (VLPs) and the recruitment of other viral proteins to the budding site was improved by the D184N mutation in guinea pig cells, which resulted in the higher infectivity of VP40 D184N -induced infectious VLPs (iVLPs) compared to that of VP40-induced iVLPs. In addition, the function of VP40 in suppressing viral RNA synthesis was influenced by the D184N mutation specifically in guinea pig cells, thus allowing greater rates of transcription and replication. Our results showed that the improved viral fitness of rMARV VP40(D184N) in guinea pig cells was due to the better viral assembly function of VP40 D184N and its lower inhibitory effect on viral transcription and replication rather than modulation of the VP40-mediated suppression of IFN signaling. IMPORTANCEThe increased virulence achieved by virus passaging in a new host was accompanied by mutations in the viral genome. Analyzing how these mutations affect the functions of viral proteins and the ability of the virus to grow within new host cells helps in the understanding of the molecular mechanisms increasing virulence. Using a reverse genetics approach, we demonstrated that a single mutation in MARV VP40 detected in a guinea pig-adapted MARV provided a replicative advantage of rMARV VP40(D184N) in guinea pig cells. Our studies show that this replicative advantage of rMARV VP40 D184N was based on the improved functions of VP40 in iVLP assembly and in the regulation of transcription and replication rather than on the ability of VP40 to combat the host innate immunity. F iloviruses, including Ebolaviruses (EBOV) and Marburg virus (MARV), are enveloped, nonsegmented, negative-strand RNA viruses (1). These viruses are known to cause severe fevers in humans and nonhuman primates, with case fatality rates of up to 90% (2). Although several antivirals and vaccines currently are being tested in clinical studies, none of them are licensed for human use. Therefore, work with filoviruses is restricted to biosafety level 4 (BSL-4) facilities. The recent EBOV outbreak in Guinea, Sierra Leone, and Liberia demonstrated the ...

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Residue 41 of the Eurasian Avian-Like Swine Influenza A Virus Matrix Protein Modulates Virion Filament Length and Efficiency of Contact Transmission

Cited by 33 publications

References 44 publications

The Interplay between the Host Receptor and Influenza Virus Hemagglutinin and Neuraminidase

The Interplay between the Host Receptor and Influenza Virus Hemagglutinin and Neuraminidase

Mammalian adaptation of influenza A(H7N9) virus is limited by a narrow genetic bottleneck

A Single Amino Acid Change in the Marburg Virus Matrix Protein VP40 Provides a Replicative Advantage in a Species-Specific Manner

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