Localization of influenza virus proteins to nuclear dot 10 structures in influenza virus-infected cells

Sato, Yoshiko; Yoshioka, Kenichi; Suzuki, Chie; Awashima, Satoshi; Hosaka, Yasuhiro; Yewdell, Jonathan W.; Kuroda, Kensuke

doi:10.1016/s0042-6822(03)00104-1

Cited by 28 publications

(27 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The cellular localization of NS1 observed in our analyses appeared to be preferentially cytoplasmic, in contrast with previous studies that have shown a preferentially nuclear localization for NS1 (60)(61)(62)(63). Nevertheless, we observed the same cellular distribution of NS1 in cells expressing the non-SUMOylatable form of NS1 as well as in cells coexpressing the ASL, therefore conclusively indicating that dramatic changes in the percentage of SUMOylated NS1 in the cell do not translate into changes in its cellular distribution.…”

Section: Discussioncontrasting

confidence: 91%

“…Different intracellular localization patterns, including nucleolar, nuclear, at promyelocytic leukemia nuclear bodies (PMLNBs), and cytoplasmic, have been assigned to NS1 (60)(61)(62)(63), thus leading to the idea that NS1's cellular localization might be dependent on numerous factors, including the possible involvement of cellular factors (19). Since SUMOylation is known to affect the cellular localization of numerous SUMO targets, including that of several viral proteins (64-67), we decided to assess whether SUMOylation could be one of the cellular factors affecting NS1's cellular localization.…”

Section: Ns1 Sumoylation Affects Viral Growth In Ifn-competent and Ifmentioning

confidence: 99%

See 1 more Smart Citation

SUMOylation Affects the Interferon Blocking Activity of the Influenza A Nonstructural Protein NS1 without Affecting Its Stability or Cellular Localization

Santos

Pal

Chacon

et al. 2013

J Virol

View full text Add to dashboard Cite

Our pioneering studies on the interplay between the small ubiquitin-like modifier (SUMO) and influenza A virus identified the nonstructural protein NS1 as the first known SUMO target of influenza virus and one of the most abundantly SUMOylated influenza virus proteins. Here, we further characterize the role of SUMOylation for the A/Puerto Rico/8/1934 (PR8) NS1 protein, demonstrating that NS1 is SUMOylated not only by SUMO1 but also by SUMO2/3 and mapping the main SUMOylation sites in NS1 to residues K219 and K70. Furthermore, by using SUMOylatable and non-SUMOylatable forms of NS1 and an NS1-specific artificial SUMO ligase (ASL) that increases NS1 SUMOylation ϳ4-fold, we demonstrate that SUMOylation does not affect the stability or cellular localization of PR8 NS1. However, NS1's ability to be SUMOylated appears to affect virus multiplication, as indicated by the delayed growth of a virus expressing the non-SUMOylatable form of NS1 in the interferon (IFN)-competent MDCK cell line. Remarkably, while a non-SUMOylatable form of NS1 exhibited a substantially diminished ability to neutralize IFN production, increasing NS1 SUMOylation beyond its normal levels also exerted a negative effect on its IFN-blocking function. This observation indicates the existence of an optimal level of NS1 SUMOylation that allows NS1 to achieve maximal activity and suggests that the limited amount of SUMOylation normally observed for most SUMO targets may correspond to an optimal level that maximizes the contribution of SUMOylation to protein function. Finally, protein cross-linking data suggest that SUMOylation may affect NS1 function by regulating the abundance of NS1 dimers and trimers in the cell.

show abstract

Section: Discussioncontrasting

confidence: 91%

Section: Ns1 Sumoylation Affects Viral Growth In Ifn-competent and Ifmentioning

confidence: 99%

SUMOylation Affects the Interferon Blocking Activity of the Influenza A Nonstructural Protein NS1 without Affecting Its Stability or Cellular Localization

Santos

Pal

Chacon

et al. 2013

J Virol

View full text Add to dashboard Cite

show abstract

“…The orthomyxovirus influenza A virus-encoded matrix 1 protein (M1) has also been reported to be coupled with ND10 during infection with unknown consequences (51,52). M1 is the most abundant viral protein both in the virion (ϳ3000 molecules/ virion) and in the cell during infection.…”

Section: During Infection Viral Proteins Target Cellular Pathways Thmentioning

confidence: 99%

“…1B). M1 protein has been shown to associate with PML nuclear body proteins (51,52), and Daxx has been shown to repress RelB (38,39). Thus, during early infection of influenza A (2-8 h.p.i.…”

Section: Involvement Of M1 In Transcription Regulation Of Antiapop-mentioning

confidence: 99%

Phosphorylation Drives an Apoptotic Protein to Activate Antiapoptotic Genes

Halder

Bhowmick

Mukherjee

et al. 2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Influenza A matrix 1 protein (M1) associates with nuclear domain 10 (ND10) early in infection. Results: Phosphorylated M1 upon nuclear translocation induces survival genes by inhibiting death domain-associated protein 6 (Daxx) of ND10. Conclusion: M1 in early infection exhibits phosphorylation-dependent antiapoptotic function. Significance: This study uncovers the antiapoptotic role of M1 and identifies a possible therapeutic target to limit virus infection.

show abstract

“…The results showing that Fyn-GFP fusion proteins efficiently transport to the plasma membrane but fail to produce any detectable GFP particles also support the statement of M1 having an inherent budding ability. Our observation that M1, in the absence of other viral proteins, was primarily targeted to the nucleus/perinuclear region initially came as a surprise but seems logical since M1 contains a well-documented nuclear signal, as demonstrated by several previous studies involving different approaches (1,51,57,67). It should be noted that our documented findings on M1 localization differ substantially from those reported previously using the M1-expressing vaccinia virus system (10,25,67).…”

Section: Discussioncontrasting

confidence: 43%

The Lack of an Inherent Membrane Targeting Signal Is Responsible for the Failure of the Matrix (M1) Protein of Influenza A Virus To Bud into Virus-Like Particles

Wang¹,

Harmon

Jin³

et al. 2010

J Virol

View full text Add to dashboard Cite

The matrix protein (M1) of influenza A virus is generally viewed as a key orchestrator in the release of influenza virions from the plasma membrane during infection. In contrast to this model, recent studies have indicated that influenza virus requires expression of the envelope proteins for budding of intracellular M1 into virus particles. Here we explored the mechanisms that control M1 budding. Similarly to previous studies, we found that M1 by itself fails to form virus-like-particles (VLPs). We further demonstrated that M1, in the absence of other viral proteins, was preferentially targeted to the nucleus/perinuclear region rather than to the plasma membrane, where influenza virions bud. Remarkably, we showed that a 10-residue membrane targeting peptide from either the Fyn or Lck oncoprotein appended to M1 at the N terminus redirected M1 to the plasma membrane and allowed M1 particle budding without additional viral envelope proteins. To further identify a functional link between plasma membrane targeting and VLP formation, we took advantage of the fact that M1 can interact with M2, unless the cytoplasmic tail is absent. Notably, native M2 but not mutant M2 effectively targeted M1 to the plasma membrane and produced extracellular M1 VLPs. Our results suggest that influenza virus M1 may not possess an inherent membrane targeting signal. Thus, the lack of efficient plasma membrane targeting is responsible for the failure of M1 in budding. This study highlights the fact that interactions of M1 with viral envelope proteins are essential to direct M1 to the plasma membrane for influenza virus particle release.The late phase of the influenza A virus replication cycle is marked by the occurrence of assembly and budding at the plasma membrane of infected cells, which leads to the separation of virion and host cell membranes and ultimately results in the production of infectious virus particles. This critical step is a highly concerted process driven largely by protein-protein, protein-lipid, and protein-nucleic acid interactions (34, 40). It has been established for many years that four viral structural components, namely, the matrix protein (M1), hemagglutinin (HA), neuraminidase (NA), and M2, are actively involved in the assembly and budding process (34,35,40), although the identities of these inter-and intramolecular interactions and regulatory mechanisms for influenza A virus assembly and budding are unclear. It has also been suggested that interactions of M1 with various cytoplasmic tails (CTs) of HA, NA, and M2 are critical to drive the assembly and release of influenza A virions from the surface of infected cells (1,5,10,18,25,29,30,68). To date, these interactions have been largely speculative because direct interactions have been demonstrated only for M1 and M2 (5, 18, 29).Early investigations into the budding machinery of influenza A virus using vaccinia virus-and baculovirus-based expression systems indicated that M1 was the only viral protein absolutely required for the assembly of virus particles (14,15...

show abstract

Localization of influenza virus proteins to nuclear dot 10 structures in influenza virus-infected cells

Cited by 28 publications

References 70 publications

SUMOylation Affects the Interferon Blocking Activity of the Influenza A Nonstructural Protein NS1 without Affecting Its Stability or Cellular Localization

SUMOylation Affects the Interferon Blocking Activity of the Influenza A Nonstructural Protein NS1 without Affecting Its Stability or Cellular Localization

Phosphorylation Drives an Apoptotic Protein to Activate Antiapoptotic Genes

The Lack of an Inherent Membrane Targeting Signal Is Responsible for the Failure of the Matrix (M1) Protein of Influenza A Virus To Bud into Virus-Like Particles

Contact Info

Product

Resources

About