Proteome Response of Chicken Embryo Fibroblast Cells to Recombinant H5N1 Avian Influenza Viruses with Different Neuraminidase Stalk Lengths

Li, Yongtao; Fan, Ming; Huang, Huimin; Guo, Kelei; Chen, Huanchun; Jin, Meilin; Zhou, Hongbo

doi:10.1038/srep40698

Cited by 15 publications

(12 citation statements)

References 40 publications

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“…7 ). In addition, altered proteins are found in other viral infections, including porcine reproductive and respiratory syndrome virus ( 75 ), H5N1 avian influenza viruses ( 76 , 77 ), Japanese encephalitis virus ( 54 ), Rift Valley fever virus ( 78 ), Hepatitis B virus ( 79 ), HIV ( 80 – 82 ), Herpes Simplex virus ( 83 ), and Epstein-Barr virus infection ( Fig. 7B and STRING ontology analysis).…”

Section: Resultsmentioning

confidence: 99%

An Autoantigen Atlas from Human Lung HFL1 Cells Offers Clues to Neurological and Diverse Autoimmune Manifestations of COVID-19

Wang¹,

Zhang

Mw³

et al. 2021

Preprint

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COVID-19 is accompanied by a myriad of both transient and long-lasting autoimmune responses. Dermatan sulfate (DS), a glycosaminoglycan crucial for wound healing, has unique affinity for autoantigens (autoAgs) from apoptotic cells. DS-autoAg complexes are capable of stimulating autoreactive B cells and autoantibody production. Using DS affinity, we identified an autoantigenome of 408 proteins from human fetal lung fibroblast HFL11 cells, at least 231 of which are known autoAgs. Comparing with available COVID data, 352 proteins of the autoantigenome have thus far been found to be altered at protein or RNA levels in SARS-Cov-2 infection, 210 of which are known autoAgs. The COVID-altered proteins are significantly associated with RNA metabolism, translation, vesicles and vesicle transport, cell death, supramolecular fibrils, cytoskeleton, extracellular matrix, and interleukin signaling. They offer clues to neurological problems, fibrosis, smooth muscle dysfunction, and thrombosis. In particular, 150 altered proteins are related to the nervous system, including axon, myelin sheath, neuron projection, neuronal cell body, and olfactory bulb. An association with the melanosome is also identified. The findings from our study illustrate a strong connection between viral infection and autoimmunity. The vast number of COVID-altered proteins with propensity to become autoAgs offers an explanation for the diverse autoimmune complications in COVID patients. The variety of autoAgs related to mRNA metabolism, translation, and vesicles raises concerns about potential adverse effects of mRNA vaccines. The COVID autoantigen atlas we are establishing provides a detailed molecular map for further investigation of autoimmune sequelae of the pandemic.Summary sentenceAn autoantigenome by dermatan sulfate affinity from human lung HFL1 cells may explain neurological and autoimmune manifestations of COVID-19

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Section: Resultsmentioning

confidence: 99%

An Autoantigen Atlas from Human Lung HFL1 Cells Offers Clues to Neurological and Diverse Autoimmune Manifestations of COVID-19

Wang¹,

Zhang

Mw³

et al. 2021

Preprint

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“…The actin and microtubule have significant roles in every virus life cycle. Viruses have ability to reorganize the cytoskeleton and restructure the host transport equipment to fulfill their needs [ 32 ], for instance, H5N1 could manipulate and exploit diverse host cytoskeletal protein to promote their infection [ 33 ]. AcMNPV has been reported to harness actin polymerization based motility in two infection phases.…”

Section: Discussionmentioning

confidence: 99%

Quantitative phosphoproteome on the silkworm (Bombyx mori) cells infected with baculovirus

Shobahah

Xue

et al. 2017

Virol J

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Background Bombyx mori has become an important model organism for many fundamental studies. Bombyx mori nucleopolyhedrovirus (BmNPV) is a significant pathogen to Bombyx mori, yet also an efficient vector for recombinant protein production. A previous study indicated that acetylation plays many vital roles in several cellular processes of Bombyx mori while global phosphorylation pattern upon BmNPV infection remains elusive.MethodEmploying tandem mass tag (TMT) labeling and phosphorylation affinity enrichment followed by high-resolution LC-MS/MS analysis and intensive bioinformatics analysis, the quantitative phosphoproteome in Bombyx mori cells infected by BmNPV at 24 hpi with an MOI of 10 was extensively examined.ResultsTotally, 6480 phosphorylation sites in 2112 protein groups were identified, among which 4764 sites in 1717 proteins were quantified. Among the quantified proteins, 81 up-regulated and 25 down-regulated sites were identified with significant criteria (the quantitative ratio above 1.3 was considered as up-regulation and below 0.77 was considered as down-regulation) and with significant p-value (p < 0.05). Some proteins of BmNPV were also hyperphosphorylated during infection, such as P6.9, 39 K, LEF-6, Ac58-like protein, Ac82-like protein and BRO-D.ConclusionThe phosphorylated proteins were primary involved in several specific functions, out of which, we focused on the binding activity, protein synthesis, viral replication and apoptosis through kinase activity.

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“…The replication kinetics results indicated that the nine strains had good growth and replication capacities on the CEF and DEF cells (Figure 2) and in chicken embryos (data not shown), however, rSNA+ and rSNA-50 showed better replication capacities in chicken embryos than the other recombinant viruses (data not shown), indicating that the ability of the viruses to replicate in vitro is affected by the control of the glycosylation sites, in addition to the length of the NA. Partial alterations in the NA stalk did not affect viral growth in the tissues and cells, however, the complete absence of the stalk presented a clear attenuated phenotype (Castrucci and Kawaoka, 1993;Li et al, 2017). The balance of HA and NA is an important factor for maintaining virus proliferation, and alterations in NA length will rebalance this activity.…”

Section: Discussionmentioning

confidence: 97%

Truncation or Deglycosylation of the Neuraminidase Stalk Enhances the Pathogenicity of the H5N1 Subtype Avian Influenza Virus in Mallard Ducks

et al. 2020

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H5N1 subtype avian influenza virus (AIV) with a deletion of 20 amino acids at residues 49-68 in the stalk region of neuraminidase (NA) became a major epidemic virus. To determine the effect of truncation or deglycosylation of the NA stalk on virulence, we used site-directed mutagenesis to insert 20 amino acids in the short-stalk virus A/mallard/Huadong/S/2005 (SY) to recover the long-stalk virus (rSNA+). A series of short-stalk or deglycosylated-stalk viruses were also constructed basing on the longstalk virus, and then the characteristics and pathogenicity of the resulting viruses were evaluated. The results showed that most of the short-stalk or deglycosylatedstalk viruses had smaller plaques, and increased thermal and low-pH stability, and a decreased neuraminidase activity when compared with the virus rSNA+. In a mallard ducks challenge study, most of the short-stalk or deglycosylated-stalk viruses showed increased pathological lesions and virus titers in the organ tissues and increased virus shedding in the oropharynx and cloaca when compared with the rSNA+ virus, while most of the short-stalk viruses, especially rSNA-20, showed higher pathogenicity than the deglycosylated-stalk virus. In addition, the short-stalk viruses showed a significantly upregulated expression of the immune-related factors in the lungs of the infected mallard ducks, including IFN-α, Mx1, and IL-8. The results suggested that NA stalk truncation or deglycosylation increases the pathogenicity of H5N1 subtype AIV in mallard ducks, which will provide a pre-warning for prevention and control of H5N1 subtype avian influenza in the waterfowl.

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Proteome Response of Chicken Embryo Fibroblast Cells to Recombinant H5N1 Avian Influenza Viruses with Different Neuraminidase Stalk Lengths

Cited by 15 publications

References 40 publications

An Autoantigen Atlas from Human Lung HFL1 Cells Offers Clues to Neurological and Diverse Autoimmune Manifestations of COVID-19

An Autoantigen Atlas from Human Lung HFL1 Cells Offers Clues to Neurological and Diverse Autoimmune Manifestations of COVID-19

Quantitative phosphoproteome on the silkworm (Bombyx mori) cells infected with baculovirus

Truncation or Deglycosylation of the Neuraminidase Stalk Enhances the Pathogenicity of the H5N1 Subtype Avian Influenza Virus in Mallard Ducks

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