Influenza A virus-encoded NS1 virulence factor protein inhibits innate immune response by targeting IKK

Gao, Shan; Song, Liping; Li, Jiandong; Zhang, Zhenzhu; Peng, Haiyan; Jiang, Wei; Wang, Qingtao; Kang, Tiebang; Chen, Shuai; Huang, Wenlin

doi:10.1111/cmi.12005

Cited by 88 publications

(92 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Commercial reporter plasmids include NF-B-Luc (Stratagene, La Jolla, CA) and RL-TK plasmid (Promega). Gift plasmids include the following: pCMV-p65-Flag (60), pFlag-IKK␤ (61), pHA-IKK␣ (62), and pXP2-p-IL-8-Luc (63).…”

Section: Methodsmentioning

confidence: 99%

Herpes Simplex Virus 1 Protein Kinase US3 Hyperphosphorylates p65/RelA and Dampens NF-κB Activation

Wang

et al. 2014

J Virol

View full text Add to dashboard Cite

Nuclear factor B (NF-B) plays important roles in innate immune responses by regulating the expression of a large number of target genes involved in the immune and inflammatory response, apoptosis, cell proliferation, differentiation, and survival. To survive in the host cells, viruses have evolved multiple strategies to evade and subvert the host immune response. Herpes simplex virus 1 (HSV-1) bears a large DNA genome, with the capacity to encode many different viral proteins to counteract the host immune responses. In the present study, we demonstrated that HSV-1 protein kinase US3 significantly inhibited NF-B activation and decreased the expression of inflammatory chemokine interleukin-8 (IL-8). US3 was also shown to hyperphosphorylate p65 at serine 75 and block its nuclear translocation. Two US3 mutants, K220M and D305A, still interacted with p65; however, they could not hyperphosphorylate p65, indicating that the kinase activity of US3 was indispensable for the function. The attenuation of NF-B activation by HSV-1 US3 protein kinase may represent a critical adaptation to enable virus persistence within the host. IMPORTANCEThis study demonstrated that HSV-1 protein kinase US3 significantly inhibited NF-B activation and decreased the expression of inflammatory chemokine interleukin-8 (IL-8). US3 hyperphosphorylated p65 at serine 75 to inhibit NF-B activation. The kinase activity of US3 was indispensable for its hyperphosphorylation of p65 and abrogation of the nuclear translocation of p65. The present study elaborated a novel mechanism of HSV-1 US3 to evade the host innate immunity.

show abstract

Section: Methodsmentioning

confidence: 99%

Herpes Simplex Virus 1 Protein Kinase US3 Hyperphosphorylates p65/RelA and Dampens NF-κB Activation

Wang

et al. 2014

J Virol

View full text Add to dashboard Cite

show abstract

“…Commercial reporter plasmids include NF-B-Luc (Stratagene, La Jolla, CA) and pRL-TK plasmid (Promega). Gift plasmids include the following: pEFIRES-HA-Ub, pEFIRES-HA-Ub(K48), and pEFIRES-HAUb(K63), obtained from Yossi Yarden (Weizmann Institute, Israel); pcDNA3-NIK (where NIK is NF-B-inducing kinase) (45); pFlag-p65 (46); pFlag-p50 (47); pFlag-IKK␤ (48); pHA-IKK␣ (49); pGL3-p-IL-6-Luc (where IL-6 is interleukin 6); and pXP2-p-IL-8-Luc (50).…”

Section: Methodsmentioning

confidence: 99%

Herpes Simplex Virus 1 E3 Ubiquitin Ligase ICP0 Protein Inhibits Tumor Necrosis Factor Alpha-Induced NF-κB Activation by Interacting with p65/RelA and p50/NF-κB1

Zhang

Wang

et al. 2013

J Virol

View full text Add to dashboard Cite

“…Some mutations in the M gene segment have been associated with transmission (20), while NP mutations control the interactions with MxA, a host-derived antiviral molecule (21). Mutations in the NS1 gene control a variety of host-specific functions and innate immune responses (22,23). Despite the identification of these mutations, we lack a complete understanding of the factors that control specific virus host range, particularly in nature, or of the host barriers that regulate the transfer of viruses to new hosts.…”

mentioning

confidence: 99%

Equine and Canine Influenza H3N8 Viruses Show Minimal Biological Differences Despite Phylogenetic Divergence

Feng

Gonzalez

Deng

et al. 2015

J Virol

View full text Add to dashboard Cite

The A/H3N8 canine influenza virus (CIV) emerged from A/H3N8 equine influenza virus (EIV) around the year 2000 through the transfer of a single virus from horses to dogs. We defined and compared the biological properties of EIV and CIV by examining their genetic variation, infection, and growth in different cell cultures, receptor specificity, hemagglutinin (HA) cleavage, and infection and growth in horse and dog tracheal explant cultures. Comparison of sequences of viruses from horses and dogs revealed mutations that may be linked to host adaptation and tropism. We prepared infectious clones of representative EIV and CIV strains that were similar to the consensus sequences of viruses from each host. The rescued viruses, including HA and neuraminidase (NA) double reassortants, exhibited similar degrees of long-term growth in MDCK cells. Different host cells showed various levels of susceptibility to infection, but no differences in infectivity were seen when comparing viruses. All viruses preferred ␣2-3-over ␣2-6-linked sialic acids for infections, and glycan microarray analysis showed that EIV and CIV HA-Fc fusion proteins bound only to ␣2-3-linked sialic acids. Cleavage assays showed that EIV and CIV HA proteins required trypsin for efficient cleavage, and no differences in cleavage efficiency were seen. Inoculation of the viruses into tracheal explants revealed similar levels of infection and replication by each virus in dog trachea, although EIV was more infectious in horse trachea than CIV. IMPORTANCEInfluenza A viruses can cross species barriers and cause severe disease in their new hosts. Infections with highly pathogenic avian H5N1 virus and, more recently, avian H7N9 virus have resulted in high rates of lethality in humans. Unfortunately, our current understanding of how influenza viruses jump species barriers is limited. Our aim was to provide an overview and biological characterization of H3N8 equine and canine influenza viruses using various experimental approaches, since the canine virus emerged from horses approximately 15 years ago. We showed that although there were numerous genetic differences between the equine and canine viruses, this variation did not result in dramatic biological differences between the viruses from the two hosts, and the viruses appeared phenotypically equivalent in most assays we conducted. These findings suggest that the crossspecies transmission and adaptation of influenza viruses may be mediated by subtle changes in virus biology. Influenza A viruses are maintained in aquatic birds as intestinal infections, occasionally transfer to and become established as respiratory infections in mammals, including humans, and sometimes spread from one mammal to another (1, 2). Mammalian hosts that have been commonly seen to maintain avian-derived viruses include swine, horses, humans, mink, seals, and, recently, dogs (2-5). Host transfers between different birds, from birds to mammals, or between different mammalian hosts are relatively common but mostly result in single infe...

show abstract

Influenza A virus-encoded NS1 virulence factor protein inhibits innate immune response by targeting IKK

Cited by 88 publications

References 66 publications

Herpes Simplex Virus 1 Protein Kinase US3 Hyperphosphorylates p65/RelA and Dampens NF-κB Activation

Herpes Simplex Virus 1 Protein Kinase US3 Hyperphosphorylates p65/RelA and Dampens NF-κB Activation

Herpes Simplex Virus 1 E3 Ubiquitin Ligase ICP0 Protein Inhibits Tumor Necrosis Factor Alpha-Induced NF-κB Activation by Interacting with p65/RelA and p50/NF-κB1

Equine and Canine Influenza H3N8 Viruses Show Minimal Biological Differences Despite Phylogenetic Divergence

Contact Info

Product

Resources

About