Abstract:
:Porcine reproductive and respiratory syndrome virus (PRRSV) infects alveolar macrophages (AMϕ), causing dysregulated alpha interferon (IFN-α) and tumor necrosis factor alpha (TNF-α) production through a mechanism(s) yet to be resolved. Here, we show that AMϕ infected with PRRSV secreted a reduced quantity of IFN-α following exposure of the cell to synthetic double-stranded RNA (dsRNA). This reduction did not correlate with reduced IFNA1 gene transcription. Rather, it coincided with two events that occurred late during infection and that were indicative of translational attenuation, specifically, the activation of eukaryotic translation initiation factor 2α (eIF2α) and the appearance of stress granules. Notably, the typical rapid production of TNF-α by AMϕ exposed to lipopolysaccharide (LPS) was suppressed or enhanced by PRRSV, depending on when the LPS exposure occurred after virus infection. If exposure was delayed until 6 h postinfection (hpi) so that the development of the cytokine response coincided with the time in which phosphorylation of eIF2α by the stress sensor PERK (protein kinase RNA [PKR]-like ER kinase) occurred, inhibition of TNF-α production was observed. However, if LPS exposure occurred at 2 hpi, prior to a detectable onset of eIF2α phosphorylation, a synergistic response was observed due to the earlier NF-κB activation via the stress sensor IRE1α (inositol-requiring kinase 1α). These results suggest that the asynchronous actions of two branches of the unfolded protein response (UPR), namely, IRE1α, and PERK, activated by ER stress resulting from the virus infection, are associated with enhancement or suppression of TNF-α production, respectively.IMPORTANCE The activation of AMϕ is controlled by the microenvironment to deter excessive proinflammatory cytokine responses to microbes that could impair lung function. However, viral pneumonias frequently become complicated by secondary bacterial infections, triggering severe inflammation, lung dysfunction, and death. Although dysregulated cytokine production is considered an integral component of the exacerbated inflammatory response in viral-bacterial coinfections, the mechanism responsible for this event is unknown. Here, we show that PRRSV replication in porcine AMϕ triggers activation of the IRE1α branch of the UPR, which causes a synergistic TNF-α response to LPS exposure. Thus, the severe pneumonias typically observed in pigs afflicted with PRRSV-bacterial coinfections could result from dysregulated, overly robust TNF-α production in response to opportunistic pathogens that is not commensurate with the typical restrained reaction by uninfected AMϕ. This notion could help in the design of therapies to mitigate the severity of viral and bacterial coinfections.
journal_name
J Viroljournal_title
Journal of virologyauthors
Chen WY,Schniztlein WM,Calzada-Nova G,Zuckermann FAdoi
10.1128/JVI.01251-17subject
Has Abstractpub_date
2018-01-02 00:00:00issue
2eissn
0022-538Xissn
1098-5514pii
JVI.01251-17journal_volume
92pub_type
杂志文章abstract::Certain chicken cells that do not spontaneously release virus particles have been shown to produce a subgroup E avian RNA tumor virus, Rous-associated virus 60 (RAV-60), after infection with viruses of other subgroups. The nucleic acids of RAV-60 were analyzed for sequence homologies with the viral nucleic acids conta...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.15.6.1367-1377.1975
更新日期:1975-06-01 00:00:00
abstract::Rotaviruses are the leading etiological agents of acute gastroenteritis in infants and young children worldwide. These nonenveloped viruses enter cells using different types of endocytosis and, depending on the virus strain, travel to different endosomal compartments before exiting to the cytosolic space. In this Gem,...
journal_title:Journal of virology
pub_type: 杂志文章,评审
doi:10.1128/JVI.01787-14
更新日期:2015-01-15 00:00:00
abstract::Examination of the interaction between human immunodeficiency virus (HIV) regulatory gene products and the host immune system is fundamental to understanding the pathogenesis of HIV and could reveal possible targets for therapeutic intervention in the treatment of AIDS. The HIV Tat gene is a potential candidate for th...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.12.7622-7629.1995
更新日期:1995-12-01 00:00:00
abstract::Infection of neonatal mice with lymphocytic choriomeningitis virus (LCMV) strain Armstrong (ARM) results in a lifelong persistent infection. Viral variants (cytotoxic T lymphocyte [CTL] negative, persistence positive [CTL- P+]) can be isolated from the lymphoid tissues of such mice. Adult mice inoculated with these CT...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.11.7367-7373.1994
更新日期:1994-11-01 00:00:00
abstract::The pathway of envelopment and egress of the varicella-zoster virus (VZV) and the primary site of viral production within the epidermal layer of the skin are not fully understood. There are several hypotheses to explain how the virus may receive an envelope as it travels to the surface of the monolayer. In this study,...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.8.4994-5010.1995
更新日期:1995-08-01 00:00:00
abstract::The interrelationship of viral ribonucleic acid (RNA) and protein synthesis in cells infected by Sindbis virus was investigated. When cultures were treated with puromycin early in the course of infection, the synthesis of interjacent RNA (26S) was preferentially inhibited. A similar result was obtained by shifting cel...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.4.2.117-122.1969
更新日期:1969-08-01 00:00:00
abstract::The induction of a unique macrophage procoagulant molecule by murine hepatitis virus strain 3 correlates with the severity of viral hepatitis. The role of tyrosine phosphorylation in the signalling pathway leading to procoagulant expression was studied. Murine hepatitis virus strain 3 initiated a rapid increase in pho...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.9.5824-5828.1995
更新日期:1995-09-01 00:00:00
abstract::Epstein-Barr virus (EBV) transforms B lymphocytes through the expression of the latent viral proteins EBNA and latent membrane protein (LMP). Recently, it has become apparent that microRNAs (miRNAs) also contribute to EBV's oncogenic properties; recombinant EBVs that lack the BHRF1 miRNA cluster display a reduced abil...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.05100-11
更新日期:2011-10-01 00:00:00
abstract::The small and middle T (tumor) antigens of polyomavirus have been shown previously to associate with the 36-kDa catalytic subunit and the 63-kDa regulatory subunit of protein phosphatase type 2A, apparently substituting for a normal third 55-kDa regulatory subunit (D.C. Pallas, L.K. Shahrik, B.L. Martin, S. Jaspers, T...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.2.886-893.1992
更新日期:1992-02-01 00:00:00
abstract::The product of the human cytomegalovirus (HCMV) UL71 gene is conserved throughout the herpesvirus family. During HCMV infection, protein pUL71 is required for efficient virion egress and is involved in the final steps of secondary envelopment leading to infectious viral particles. We found strong indications for oligo...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.06556-11
更新日期:2012-03-01 00:00:00
abstract::Paramyxoviral RNAs are synthesized by a viral RNA-dependent RNA polymerase (RdRp) consisting of the large (L) protein and its cofactor phosphoprotein (P protein). The L protein is a multifunctional protein that catalyzes RNA synthesis, mRNA capping, and mRNA polyadenylation. Growing evidence shows that the stability o...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02220-16
更新日期:2017-02-28 00:00:00
abstract::The Aichi virus 2A protein is not a protease, unlike many other picornavirus 2A proteins, and it is related to a cellular protein, H-rev107. Here, we examined the replication properties of two 2A mutants in Vero cells and a cell-free translation/replication system. In one mutant, amino acids 36 to 126 were replaced wi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01051-08
更新日期:2008-10-01 00:00:00
abstract::Rinderpest virus is a morbillivirus and is the causative agent of a widespread and important disease of cattle. The viral genome is a single strand of RNA in the negative sense. We have constructed plasmids containing cDNA copies of the 5' and 3' termini of the virus separated by a reporter gene and have shown that an...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.2.1265-1271.1997
更新日期:1997-02-01 00:00:00
abstract::The stimulation of host macromolecular synthesis and induction into the cell cycle of serum-deprived G0-G1-arrested mouse embryo fibroblasts were examined after infection of resting cells with wild-type simian virus 40 or with viral mutants affecting T antigen (tsA58) or small t antigen (dl884). At various times after...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.37.2.802-812.1981
更新日期:1981-02-01 00:00:00
abstract::Influenza A H9N2 viruses are common poultry pathogens that occasionally infect swine and humans. It has been shown previously with H9N2 viruses that reassortment can generate novel viruses with increased transmissibility. Here, we demonstrate the modeling power of a novel transfection-based inoculation system to selec...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02677-13
更新日期:2014-01-01 00:00:00
abstract::Mouse mammary tumor virus (MMTV) is a retrovirus which induces a strong immune response and a dramatic increase in the number of infected cells through the expression of a superantigen (SAg). Many cytokines are likely to be involved in the interaction between MMTV and the immune system. In particular, alpha/beta inter...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.4.2638-2646.1998
更新日期:1998-04-01 00:00:00
abstract::The features of herpes simplex virus 1 (HSV-1) strain 129 (H129), including natural neurotropism and anterograde transneuronal trafficking, make it a potential tool for anterograde neural circuitry tracing. Recently anterograde polysynaptic and monosynaptic tracers were developed from H129 and have been applied for th...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01957-19
更新日期:2020-03-31 00:00:00
abstract::Infection with severe acute respiratory syndrome coronavirus (SARS-CoV) causes acute lung injury (ALI) that often leads to severe lung disease. A mouse model of acute SARS-CoV infection has been helpful in understanding the host response to infection; however, there are still unanswered questions concerning SARS-CoV p...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01689-12
更新日期:2012-12-01 00:00:00
abstract::Mouse mammary tumor virus (MMTV) DNA fragments were cloned into M13 bacteriophage, and the single-stranded recombinant phage DNAs were used as strand-specific nucleic acid hybridization probes to measure synthesis of plus (genomic) and minus strands of MMTV RNA in cultured cell lines and in cell-free preparations of n...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.50.1.60-65.1984
更新日期:1984-04-01 00:00:00
abstract::An in vitro poliovirus RNA-synthesizing system derived from a crude membrane fraction of infected HeLa cells was used to analyze the mechanism of initiation of poliovirus plus-strand RNA synthesis. This system contains an activity that synthesizes the nucleotidyl proteins VPg-pU and VPg-pUpU. These molecules represent...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.60.1.43-53.1986
更新日期:1986-10-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00204-08
更新日期:2008-09-01 00:00:00
abstract::The mechanism by which bovine herpesvirus 1 (BHV-1) predisposes cattle to bacterial pneumonia was investigated by using an in vitro system to demonstrate immunosuppression. At a multiplicity of infection of 0.001, live or inactivated BHV-1 induced a 50% inhibition of the proliferative response of peripheral blood mono...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.9.4146-4151.1990
更新日期:1990-09-01 00:00:00
abstract::Apoptosis of infected cells is critically involved in antiviral defense. Apoptosis, however, may also support the release and spread of viruses. Although the elimination of infected hepatocytes is required to combat hepatitis B virus (HBV) infection, it is still unknown which consequences hepatocyte apoptosis has for ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00653-10
更新日期:2010-11-01 00:00:00
abstract::Epstein-Barr virus (EBV) latent membrane protein 2A (LMP2A) is widely expressed in EBV-infected cells within the infected human host and EBV-associated malignancies, suggesting that LMP2A is important for EBV latency, persistence, and EBV-associated tumorigenesis. Previously, we demonstrated that LMP2A provides an ant...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00537-07
更新日期:2007-09-01 00:00:00
abstract::The human immunodeficiency virus type 1 (HIV-1) accessory protein Nef is heavily targeted by CD8(+) T lymphocytes (CTLs) during acute infection and therefore is included in many candidate vaccines. We investigated whether CTL targeting of Nef during acute infection contributes to immune control by disrupting the funct...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00482-14
更新日期:2014-07-01 00:00:00
abstract::The Middle East respiratory syndrome coronavirus (MERS-CoV) nonstructural protein 16 (nsp16) is an S-adenosyl-l-methionine (SAM)-dependent 2'-O-methyltransferase (2'-O-MTase) that is thought to methylate the ribose 2'-OH of the first transcribed nucleotide (N1) of viral RNA cap structures. This 2'-O-MTase activity is ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02217-16
更新日期:2017-02-14 00:00:00
abstract::A host-mediated RNA-editing event allows hepatitis delta virus (HDV) to express two essential proteins, the small delta antigen (HDAg-S) and the large delta antigen (HDAg-L), from a single open reading frame. One or several members of the ADAR (adenosine deaminases that act on RNA) family are thought to convert the ad...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.75.18.8547-8555.2001
更新日期:2001-09-01 00:00:00
abstract::Resistance to erythroleukemia induced by infection with the Friend virus complex (FV) has been mapped to several genes residing both within and outside the murine major histocompatibility complex (MHC). MHC genes located in the A, D, and Qa/Tla regions of the murine H-2 complex have been shown to affect disease resist...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.8.4921-4926.1994
更新日期:1994-08-01 00:00:00
abstract::Genomic replication of the negative-strand RNA viruses is dependent upon protein synthesis. To examine the requirement for protein synthesis in replication, we developed an in vitro system that supports the genome replication of defective interfering particles of the negative-strand rhabdovirus vesicular stomatitis vi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.49.2.303-309.1984
更新日期:1984-02-01 00:00:00
abstract::Primary human embryonic kidney (HEK) cells were transformed by a focus assay with BK virus (BKV) DNA molecularly cloned at its unique EcoRI site. Both viral DNA sequences and viral tumor antigens were present and expressed in all the foci that we examined. However, cells isolated from foci were incapable of growth in ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.58.2.680-683.1986
更新日期:1986-05-01 00:00:00