H7N9: A killer in the making or a false alarm?

Nailwal, Himani; Kamra, Komal; Lal, Sunil K.

doi:10.1139/cjm-2014-0186

Cited by 4 publications

(6 citation statements)

References 52 publications

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“…Influenza A virus (IAV) by far remains the most important of all respiratory viruses, causing severe morbidity and mortality every year. 1 Nucleoprotein (NP) of IAV is a viral RNA genome-encapsulating structural protein that has been implicated in various other indispensable activities for virus replication and pathogenesis-like intracellular trafficking of the viral genome, viral RNA replication, virus assembly 2 , 3 via its interaction with a plethora of cellular factors like cytoskeleton scaffolding protein α-actinin-4, nuclear import receptor α importin, nuclear export receptor CRM1, DEAD-box helicase BAT1/UAP56 and cytoskeletal element F actin. 4 , 5 , 6 , 7 , 8…”

mentioning

confidence: 99%

The nucleoprotein of influenza A virus induces p53 signaling and apoptosis via attenuation of host ubiquitin ligase RNF43

et al. 2015

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The interplay between influenza virus and host factors to support the viral life cycle is well documented. Influenza A virus (IAV) proteins interact with an array of cellular proteins and hijack host pathways which are at the helm of cellular responses to facilitate virus invasion. The multifaceted nature of the ubiquitination pathway for protein regulation makes it a vulnerable target of many viruses including IAV. To this end we conducted a yeast two-hybrid screen to search for cellular ubiquitin ligases important for influenza virus replication. We identified host protein, RING finger protein 43 (RNF43), a RING-type E3 ubiquitin ligase, as a novel interactor of nucleoprotein (NP) of IAV and an essential partner to induce NP-driven p53-mediated apoptosis in IAV-infected cells. In this study, we demonstrate that IAV leads to attenuation of RNF43 transcripts and hence its respective protein levels in the cellular milieu whereas in RNF43 depleted cells, viral replication was escalated several folds. Moreover, RNF43 polyubiquitinates p53 which further leads to its destabilization resulting in a decrease in induction of the p53 apoptotic pathway, a hitherto unknown process targeted by NP for p53 stabilization and accumulation. Collectively, these results conclude that NP targets RNF43 to modulate p53 ubiquitination levels and hence causes p53 stabilization which is conducive to an enhanced apoptosis level in the host cells. In conclusion, our study unravels a novel strategy adopted by IAV for utilizing the much conserved ubiquitin proteasomal pathway.

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confidence: 99%

The nucleoprotein of influenza A virus induces p53 signaling and apoptosis via attenuation of host ubiquitin ligase RNF43

et al. 2015

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“…Since 2013, several hundred zoonotic infections with the H7N9 strains were reported, albeit with a lower mortality rate than infections associated with the H5N1 viruses. The human-infecting H7N9 virus contains HA and NA viral RNA segments of duck origin with the remaining segments from the H9N2 chicken-infecting virus [ 70 ]. Understanding the mechanism to switch preference for this virus is particularly important, considering some strains of this subtype already acquired the Q226L mutation.…”

Section: Adaptive Mutations Of Iav Hamentioning

confidence: 99%

OUP accepted manuscript

Łażniewski

Dawson

Szczepińska

et al. 2017

Briefings in Functional Genomics

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Hemagglutinin (HA) is a transmembrane protein of the influenza A virus and a key component in its life cycle. The protein allows the virus to enter a host cell by recognizing specific glycans attached to transmembrane proteins of the host, which leads to viral endocytosis. In recent years, significant progress has been made in understanding the structural relationship between changes in the HA receptor-binding site (RBS) and the sialylated glycans that bind them. Several mutations were identified in the HA RBS that allows the virus to change host tropism. Their impact on binding the analogs of human and avian receptors was determined with X-ray crystallography. In this article, we provide a short overview of the HA protein structure and briefly discuss the adaptive mutations introduced to different HA subtypes.

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“…Live poultry markets were identified as the main source of human infections, since most of the infected patients had been exposed to poultry. However, the novel H7N9 virus was asymptomatic in poultry, which made it difficult to detect infected farms and to identify the source and mode of transmission [ 39 , 45 , 46 ].…”

Section: Emerging Influenza Strainsmentioning

confidence: 99%

“…The novel H7N9 virus was of avian origin and phylogenetic analysis showed that it was the result of triple reassortment. The HA gene originated from the duck H7N3 subtype, the NA gene from a migratory bird H7N9 virus in Korea, and the six internal genes from poultry H9N2 viruses [ 6 , 38 , 46 , 47 ]. Domestic ducks are the intermediate host of H7N9, which is reassorted with H9N2 when transmitted to chickens [ 48 ].…”

Section: Emerging Influenza Strainsmentioning

confidence: 99%

“…It seems that H7N9 can be transmitted from poultry to humans more easily than H5N1, given that 77% of H7N9-infected patients had previously been exposed to poultry [ 46 ], while human-to-human transmission proved inefficient and difficult. Some studies have indicated a possible transmission of the novel H7N9 virus among family members; indeed, genetic factors may facilitate transmission of the virus, and potential genetic susceptibility could play an important role.…”

Section: Emerging Influenza Strainsmentioning

confidence: 99%

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Emerging Influenza Strains in the Last Two Decades: A Threat of a New Pandemic?

et al. 2015

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In the last 20 years, novel non-seasonal influenza viruses have emerged, most of which have originated from birds. Despite their apparent inability to cause pandemics, with the exception of H1N1 swine influenza virus, these viruses still constitute a constant threat to public health. While general concern has decreased after the peak of the H5N1 virus, in recent years several novel reassorted influenza viruses (e.g., H7N9, H9N2, H10N8) have jumped the host-species barrier and are under surveillance by the scientific community and public health systems. It is still unclear whether these viruses can actually cause pandemics or just isolated episodes. The purpose of this review is to provide an overview of old and novel potential pandemic strains of recent decades.

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H7N9: A killer in the making or a false alarm?

Cited by 4 publications

References 52 publications

The nucleoprotein of influenza A virus induces p53 signaling and apoptosis via attenuation of host ubiquitin ligase RNF43

The nucleoprotein of influenza A virus induces p53 signaling and apoptosis via attenuation of host ubiquitin ligase RNF43

OUP accepted manuscript

Emerging Influenza Strains in the Last Two Decades: A Threat of a New Pandemic?

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