Abstract:
:Lassa fever (LF) is a zoonotic viral hemorrhagic fever caused by Lassa virus (LASV), which is endemic to West African countries. Previous studies have suggested an important role for T-cell-mediated immunopathology in LF pathogenesis, but the mechanisms by which T cells influence disease severity and outcome are not well understood. Here, we present a multiparametric analysis of clinical immunology data collected during the 2017-2018 Lassa fever outbreak in Nigeria. During the acute phase of LF, we observed robust activation of the polyclonal T-cell repertoire, which included LASV-specific and antigenically unrelated T cells. However, severe and fatal LF cases were characterized by poor LASV-specific effector T-cell responses. Severe LF was also characterized by the presence of circulating T cells with homing capacity to inflamed tissues, including the gut mucosa. These findings in LF patients were recapitulated in a mouse model of LASV infection, in which mucosal exposure resulted in remarkably high lethality compared to skin exposure. Taken together, our findings indicate that poor LASV-specific T-cell responses and activation of nonspecific T cells with homing capacity to inflamed tissues are associated with severe LF.IMPORTANCE Lassa fever may cause severe disease in humans, in particular in areas of endemicity like Sierra Leone and Nigeria. Despite its public health importance, the pathophysiology of Lassa fever in humans is poorly understood. Here, we present clinical immunology data obtained in the field during the 2018 Lassa fever outbreak in Nigeria indicating that severe Lassa fever is associated with activation of T cells antigenically unrelated to Lassa virus and poor Lassa virus-specific effector T-cell responses. Mechanistically, we show that these bystander T cells express defined tissue homing signatures that suggest their recruitment to inflamed tissues and a putative role of these T cells in immunopathology. These findings open a window of opportunity to consider T-cell targeting as a potential postexposure therapeutic strategy against severe Lassa fever, a hypothesis that could be tested in relevant animal models, such as nonhuman primates.
journal_name
J Viroljournal_title
Journal of virologyauthors
Port JR,Wozniak DM,Oestereich L,Pallasch E,Becker-Ziaja B,Müller J,Rottstegge M,Olal C,Gómez-Medina S,Oyakhliome J,Ighodalo Y,Omomoh E,Olokor T,Adomeh DI,Asogun D,Ogbani-Emovon E,Hartmann K,Krasemann S,Nelson EV,Escdoi
10.1128/JVI.01367-20subject
Has Abstractpub_date
2020-10-14 00:00:00issue
21eissn
0022-538Xissn
1098-5514pii
JVI.01367-20journal_volume
94pub_type
杂志文章abstract::The severe acute respiratory syndrome coronavirus (SARS-CoV) was recently identified as the etiology of SARS. The virus particle consists of four structural proteins: spike (S), small envelope (E), membrane (M), and nucleocapsid (N). Recognition of a specific sequence, termed the packaging signal (PS), by a virus N pr...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.22.13848-13855.2005
更新日期:2005-11-01 00:00:00
abstract::Previous studies have shown that serum interferon (IFN) production in mice is quantitatively influenced by If loci, whose alleles determine high or low production. Although different loci influence IFN production in response to different inducers, such as Newcastle disease virus, Sendai virus, herpes simplex virus typ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.58.3.743-747.1986
更新日期:1986-06-01 00:00:00
abstract::Retroviruses and retrotransposons insert into the host genome with no obvious sequence specificity. We examined the target sites of the retroelement ZAM by sequencing each host-ZAM junction in the genome of Drosophila melanogaster. Our overall data provide compelling evidence that ZAM integration machinery recognizes ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.8.7061-7064.1999
更新日期:1999-08-01 00:00:00
abstract:UNLABELLED:Foamy viruses (FVs) are complex retroviruses that establish lifelong persistent infection without evident pathology. However, the roles of cellular factors in FV latency are poorly understood. This study revealed that N-Myc interactor (Nmi) could inhibit the replication of prototype foamy virus (PFV). Overex...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00799-14
更新日期:2014-06-01 00:00:00
abstract::Infectious bursal disease (IBD) is an acute, highly contagious, and immunosuppressive avian disease caused by IBD virus (IBDV). Although IBDV-induced host cell apoptosis has been established, the underlying molecular mechanism is still unclear. We report here that IBDV viral protein 5 (VP5) is a major apoptosis induce...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.06104-11
更新日期:2012-02-01 00:00:00
abstract::The E6 oncoprotein of high-risk human papillomavirus type 16 (HPV16) interacts with several nuclear transcription factors and coactivators in addition to cytoplasmic proteins, suggesting that nuclear import of HPV16 E6 plays a role in the cellular transformation process. In this study we have investigated the nuclear ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.4.2330-2337.2003
更新日期:2003-02-01 00:00:00
abstract::Severe acute respiratory syndrome (SARS), caused by a novel coronavirus (CoV) known as SARS-CoV, is a contagious and life-threatening respiratory illness with pneumocytes as its main target. A full understanding of how SARS-CoV would interact with lung epithelial cells will be vital for advancing our knowledge of SARS...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.15.9470-9479.2005
更新日期:2005-08-01 00:00:00
abstract::Rift Valley fever virus strain MP-12 was generated by serial plaque passages of parental strain ZH548 12 times in MRC-5 cells in the presence of a chemical mutagen, 5-fluorouracil. As a result, MP-12 encoded 4, 9, and 10 mutations in the S, M, and L segments, respectively. Among them, mutations in the M and L segments...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02081-12
更新日期:2012-12-01 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::A human cell line (293) transformed by adenovirus type 5 encodes mRNA's and proteins from the early region 1 (E1) of the viral genome. These products correspond to those synthesized early after adenovirus infection of normal cells. This pattern of expression is different from that observed at later times in the lytic ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.36.3.860-871.1980
更新日期:1980-12-01 00:00:00
abstract::The filoviruses Ebola Zaire virus and Marburg virus are believed to infect target cells through endocytic vesicles, but the details of this pathway are unknown. We used a pseudotyping strategy to investigate the cell biology of filovirus entry. We observed that specific inhibitors of the caveola system, including chol...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.10.5266-5270.2002
更新日期:2002-05-01 00:00:00
abstract::Poliovirus (PV) modifies membrane-trafficking machinery in host cells for its viral RNA replication. To date, ARF1, ACBD3, BIG1/BIG2, GBF1, RTN3, and PI4KB have been identified as host factors of enterovirus (EV), including PV, involved in membrane traffic. In this study, we performed small interfering RNA (siRNA) scr...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00114-12
更新日期:2012-05-01 00:00:00
abstract::The tetrameric paramyxovirus hemagglutinin-neuraminidase (HN) protein mediates attachment to sialic acid-containing receptors as well as cleavage of the same moiety via its neuraminidase (NA) activity. The X-ray crystallographic structure of an HN dimer from Newcastle disease virus (NDV) suggests that a single site in...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.12.6913-6922.2003
更新日期:2003-06-01 00:00:00
abstract::The adenovirus type 4 origins of replication are located at each end of the linear, protein-linked viral DNA molecule and consist of the terminal 18 bp of the viral genome. The sequence of the first 8 bp of the viral genome varies among different adenovirus serotypes, but the sequence from bp 9 to 18 is conserved in a...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.9.5037-5044.1991
更新日期:1991-09-01 00:00:00
abstract::We isolated a simian virus 40 mutant, dl2194, which carried deletions in both early genes. One deletion removed 234 base pairs in the 54/59 region within the small-t-antigen coding sequence and the large-T-antigen gene intron. The second deletion removed 57 base pairs at the C terminus of the large-T-antigen coding se...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.40.3.625-634.1981
更新日期:1981-12-01 00:00:00
abstract::A thorough understanding of the diversity of viruses in wildlife provides epidemiological baseline information about potential pathogens. Metagenomic analysis of the enteric viral flora revealed a new anellovirus and bocavirus species in pine martens and a new circovirus-like virus and geminivirus-related DNA virus in...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.06373-11
更新日期:2012-02-01 00:00:00
abstract::The outcome of a viral infection is regulated in part by the complex coordination of viral and host interactions that compete for the control and optimization of virus replication. Severe acute respiratory syndrome coronavirus (SARS-CoV) intimately engages and regulates the host innate immune responses during infectio...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02220-08
更新日期:2009-07-01 00:00:00
abstract::SARS coronavirus (SARS-CoV) encodes several unique group-specific open reading frames (ORFs) relative to other known coronaviruses. To determine the significance of the SARS-CoV group-specific ORFs in virus replication in vitro and in mice, we systematically deleted five of the eight group-specific ORFs, ORF3a, OF3b, ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.23.14909-14922.2005
更新日期:2005-12-01 00:00:00
abstract::Varicella-zoster virus DNA was digested with 11 restriction endonucleases, and the resulting fragments were separated on agarose gels. Terminal fragments were identified by lambda exonuclease digestion. Physical maps were then constructed using a combination of double restriction enzyme digestion and hybridization to ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.50.2.615-618.1984
更新日期:1984-05-01 00:00:00
abstract::ICP0 is a nuclear phosphoprotein involved in the activation of herpes simplex virus type 1 (HSV-1) gene expression during lytic infection and reactivation from viral latency. Although available evidence suggests that ICP0 acts at the level of transcription, definitive studies specifically addressing this issue have no...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.9.6850-6862.1997
更新日期:1997-09-01 00:00:00
abstract::RNA editing of the hepatitis delta virus (HDV) antigenome at the amber/W site by the host RNA adenosine deaminase ADAR1 is a critical step in the HDV replication cycle. Editing is required for production of the viral protein hepatitis delta antigen long form (HDAg-L), which is necessary for viral particle production b...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.17.11187-11193.2005
更新日期:2005-09-01 00:00:00
abstract::Syncytial (syn) mutants of herpes simplex virus cause cell fusion. Many syn mutations map to the syn1 locus, which has been identified with the gK (UL53) gene. In this work, the gK genes of eight syn mutants derived from the KOS strain were sequenced to identify residues and, possibly, domains important for the fusion...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.12.8277-8281.1994
更新日期:1994-12-01 00:00:00
abstract::Treatment with sodium dodecyl sulfate (SDS) converted the vaccinia virus strain IHD-J into particles of two types: (i) ghosts which possessed a thin-membrane vesicle derived from basement part of the virus membrane with attached lateral bodies and a membranous structure derived from the core wall and (ii) aggregates o...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.50.3.929-938.1984
更新日期:1984-06-01 00:00:00
abstract:UNLABELLED:In Kaposi's sarcoma-associated herpesvirus (KSHV), poly(ADP-ribose) polymerase 1 (PARP-1) acts as an inhibitor of lytic replication. Here, we demonstrate that KSHV downregulated PARP-1 upon reactivation. The viral processivity factor of KSHV (PF-8) interacted with PARP-1 and was sufficient to degrade PARP-1 ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00559-15
更新日期:2015-09-01 00:00:00
abstract::We investigated the features of the Moloney murine sarcoma virus leader sequence necessary for RNA packaging function by using a deletion analysis approach. We found that sequences that extend beyond those characterized genetically in previous reports are important for optimal packaging efficiency. A fragment covering...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.9.4643-4648.2002
更新日期:2002-05-01 00:00:00
abstract::Varicella-zoster virus (VZV) is distinguished from herpes simplex virus type 1 (HSV-1) by the fact that cell-to-cell fusion and syncytium formation require only gH and gL within a transient-expression system. In the HSV system, four glycoproteins, namely, gH, gL, gB, and gD, are required to induce a similar fusogenic ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.19.9483-9492.2001
更新日期:2001-10-01 00:00:00
abstract::A Sepharose 4B chromatographic method for purification of retroviruses is described which was less time consuming, increased purified virus yields, conserved viral glycoprotein, and increased recovery of biological infectivity in comparison with conventional sucrose gradient ultracentrifugation techniques. ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.25.3.923-927.1978
更新日期:1978-03-01 00:00:00
abstract:UNLABELLED:An altered intestinal microbiome during chronic human immunodeficiency virus (HIV) infection is associated with mucosal dysfunction, inflammation, and disease progression. We performed a preclinical evaluation of the safety and efficacy of fecal microbiota transplantation (FMT) as a potential therapeutic in ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00099-16
更新日期:2016-04-29 00:00:00
abstract::Although there is increasing evidence that individuals already infected with human immunodeficiency virus type 1 (HIV-1) can be infected with a heterologous strain of the virus, the extent of protection against superinfection conferred by the first infection and the biologic consequences of superinfection are not well...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02237-08
更新日期:2009-03-01 00:00:00
abstract::Hepatitis C virus (HCV), a member of the family Flaviviridae, is a leading cause of chronic liver disease and cancer. Recent advances in HCV therapeutics have resulted in improved cure rates, but an HCV vaccine is not available and is urgently needed to control the global pandemic. Vaccine development has been hampere...
journal_title:Journal of virology
pub_type: 杂志文章,评审
doi:10.1128/JVI.00874-14
更新日期:2014-09-01 00:00:00