Abstract:
:Ebola virus (EBOV) continues to pose a significant threat to human health, as evidenced by the 2013-2016 epidemic in West Africa and the ongoing outbreak in the Democratic Republic of the Congo. EBOV causes hemorrhagic fever, organ damage, and shock culminating in death, with case fatality rates as high as 90%. This high lethality combined with the paucity of licensed medical countermeasures makes EBOV a critical human pathogen. Although EBOV infection results in significant damage to the liver and the adrenal glands, little is known about the molecular signatures of injury in these organs. Moreover, while changes in peripheral blood cells are becoming increasingly understood, the host responses within organs and lymphoid tissues remain poorly characterized. To address this knowledge gap, we tracked longitudinal transcriptional changes in tissues collected from EBOV-Makona-infected cynomolgus macaques. Following infection, both liver and adrenal glands exhibited significant and early downregulation of genes involved in metabolism, coagulation, hormone synthesis, and angiogenesis; upregulated genes were associated with inflammation. Analysis of lymphoid tissues showed early upregulation of genes that play a role in innate immunity and inflammation and downregulation of genes associated with cell cycle and adaptive immunity. Moreover, transient activation of innate immune responses and downregulation of humoral immune responses in lymphoid tissues were confirmed with flow cytometry. Together, these data suggest that the liver, adrenal gland, and lymphatic organs are important sites of EBOV infection and that dysregulating the function of these vital organs contributes to the development of Ebola virus disease.IMPORTANCE Ebola virus (EBOV) remains a high-priority pathogen since it continues to cause outbreaks with high case fatality rates. Although it is well established that EBOV results in severe organ damage, our understanding of tissue injury in the liver, adrenal glands, and lymphoid tissues remains limited. We begin to address this knowledge gap by conducting longitudinal gene expression studies in these tissues, which were collected from EBOV-infected cynomolgus macaques. We report robust and early gene expression changes within these tissues, indicating they are primary sites of EBOV infection. Furthermore, genes involved in metabolism, coagulation, and adaptive immunity were downregulated, while inflammation-related genes were upregulated. These results indicate significant tissue damage consistent with the development of hemorrhagic fever and lymphopenia. Our study provides novel insight into EBOV-host interactions and elucidates how host responses within the liver, adrenal glands, and lymphoid tissues contribute to EBOV pathogenesis.
journal_name
J Viroljournal_title
Journal of virologyauthors
Jankeel A,Menicucci AR,Woolsey C,Fenton KA,Mendoza N,Versteeg K,Cross RW,Geisbert TW,Messaoudi Idoi
10.1128/JVI.00250-20subject
Has Abstractpub_date
2020-05-18 00:00:00issue
11eissn
0022-538Xissn
1098-5514pii
JVI.00250-20journal_volume
94pub_type
杂志文章abstract::Many of the approximately 165 proteins encoded by the African swine fever virus (ASFV) genome do not have significant similarity to known proteins and have not been studied experimentally. One such protein is DP148R. We showed that the DP148R gene is transcribed at early times postinfection. Deletion of this gene did ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01428-17
更新日期:2017-11-30 00:00:00
abstract::Wild-type Sindbis virus (SINV) strain MRE16 efficiently infects Aedes aegypti midgut epithelial cells (MEC), but laboratory-derived neurovirulent SINV strain TE/5'2J infects MEC poorly. SINV determinants for MEC infection have been localized to the E2 glycoprotein. The E2 amino acid sequences of MRE16 and TE/5'2J diff...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02060-07
更新日期:2008-03-01 00:00:00
abstract:UNLABELLED:The noncovalent interactions that mediate trimerization of the influenza hemagglutinin (HA) are important determinants of its biological activities. Recent studies have demonstrated that mutations in the HA trimer interface affect the thermal and pH sensitivities of HA, suggesting a possible impact on vaccin...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02278-13
更新日期:2014-05-01 00:00:00
abstract::Mammalian reoviruses are internalized into cells by receptor-mediated endocytosis. Within the endocytic compartment, the viral outer capsid undergoes acid-dependent proteolysis resulting in removal of the sigma3 protein and proteolytic cleavage of the mu1/mu1C protein. Ammonium chloride (AC) is a weak base that blocks...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.80.2.671-681.2006
更新日期:2006-01-01 00:00:00
abstract::Hepatitis C virus (HCV) is an important human pathogen associated with chronic liver disease. Recently, based on a genotype 2a isolate, tissue culture systems supporting complete replication and infectious virus production have been developed. In this study, we used cell culture-produced infectious HCV to analyze the ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.80.4.1734-1741.2006
更新日期:2006-02-01 00:00:00
abstract::The purpose of this study was to gain insights into the regulation of Epstein-Barr virus (EBV) gene transcription during the establishment of viral latency in B cells. During the early stages of EBV infection in B lymphocytes, transcription of six viral nuclear antigens (EBNAs) is initiated from an early promoter (Wp)...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.6.3561-3570.1996
更新日期:1996-06-01 00:00:00
abstract::Bacteriophage with linear, double-stranded DNA genomes package DNA into preassembled protein shells called procapsids. Located at one vertex in the procapsid is a portal complex composed of a ring of 12 subunits of portal protein. The portal complex serves as a docking site for the DNA packaging enzymes, a conduit for...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.20.10245-10255.2002
更新日期:2002-10-01 00:00:00
abstract::Nearly 50 years ago, the discovery of interferon prompted the notion that host cells innately respond to viral invasion. Since that time, technological advances have allowed this response to be extensively characterized and dissected in vitro. However, these advances have only recently been applied to highly complex, ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01936-06
更新日期:2007-02-01 00:00:00
abstract::Plasma human immunodeficiency virus type 1 (HIV-1) turnover and kinetics were studied in children aged 15 days to 2 years following the initiation of a triple antiretroviral drug regimen consisting of zidovudine, lamivudine, and nevirapine. HIV-1 turnover was at least as rapid as that previously described in adults; t...
journal_title:Journal of virology
pub_type: 临床试验,杂志文章
doi:10.1128/JVI.73.1.362-367.1999
更新日期:1999-01-01 00:00:00
abstract:UNLABELLED:Bluetongue is one of the major infectious diseases of ruminants and is caused by bluetongue virus (BTV), an arbovirus existing in nature in at least 26 distinct serotypes. Here, we describe the development of a vaccine platform for BTV. The advent of synthetic biology approaches and the development of revers...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02183-14
更新日期:2014-11-01 00:00:00
abstract::Human immunodeficiency virus type 1 (HIV-1) nucleotide sequences encoding p24Gag and the Env C2V3 region were obtained from seven patients who were selected on the basis of having paradoxical seronegativity on a subset of HIV enzyme-linked immunosorbent assay detection kits and having atypical Western blot (immunoblot...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.9.5640-5649.1995
更新日期:1995-09-01 00:00:00
abstract::Some retroviruses with an extended repeat (R) region encode the polyadenylation signal within the R region such that this signal is present at both the 5' and 3' ends of the viral transcript. This necessitates differential regulation to either repress recognition of the 5' polyadenylation signal or enhance usage of th...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.1.81-91.1999
更新日期:1999-01-01 00:00:00
abstract::A covalently closed circular form of unintegrated viral DNA obtained from NIH 3T3 cells freshly infected with Moloney murine leukemia virus (M-MLV) and a port of the endogenous M-MLV from the BALB/Mo mouse strain have been cloned in bacteriophage lambda. The unintegrated viral DNA was cleaved with restriction endonucl...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.36.1.254-263.1980
更新日期:1980-10-01 00:00:00
abstract::It has been suggested that vaccination prior to infection may direct the mutational evolution of human immunodeficiency virus type 1 (HIV-1) to a less fit virus, resulting in an attenuated course of disease. The present study was initiated to explore whether prior immunization might prevent the reversion of the virus ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01193-10
更新日期:2010-12-01 00:00:00
abstract::A versatile green fluorescent protein (GFP) expression cassette containing the replication origins of the monopartite begomovirus Tomato yellow leaf curl Sardinia virus (TYLCSV) is described. Transgenic Nicotiana benthamiana plants containing one copy of the cassette stably integrated into their genome were superinfec...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.80.7.3624-3633.2006
更新日期:2006-04-01 00:00:00
abstract::The strain of Newcastle disease virus (NDV(pi)) present in persistently infected L cells differed markedly from the Herts strain (NDV(0)) used to initiate the infection. NDV(pi) produced small plaques (less than 1 mm) in chick embryo cell cultures, whereas the wild type (NDV(0)) produced large plaques (2 to 3 mm). The...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.4.3.244-251.1969
更新日期:1969-09-01 00:00:00
abstract::Regulatory T (T(R)) cells maintain tolerance to self-antigens and control immune responses to alloantigens after organ transplantation. Here, we show that CD4(+) CD25(+) human T(R) cells suppress virus-specific T-cell responses. Depletion of T(R) cells from peripheral blood mononuclear cells enhances T-cell responses ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.78.5.2454-2459.2004
更新日期:2004-03-01 00:00:00
abstract::Human metapneumovirus (hMPV) is a leading cause of viral lower respiratory tract infection in children. The sole target of neutralizing antibodies targeting hMPV is the fusion (F) protein, a class I viral fusion protein mediating virus-cell membrane fusion. There have been several monoclonal antibodies (mAbs) isolated...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00342-19
更新日期:2019-09-12 00:00:00
abstract::Recent in vitro proteomics screens revealed that many host proteins could interact with the replication proteins of Tomato bushy stunt virus (TBSV), which is a small, plus-stranded RNA virus (Z. Li, D. Barajas, T. Panavas, D. A. Herbst, and P. D. Nagy, J. Virol. 82:6911-6926, 2008). To further our understanding of the...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00789-09
更新日期:2009-11-01 00:00:00
abstract::We investigated the cis-acting sequences involved in termination of vesicular stomatis virus mRNA synthesis by using bicistronic genomic analogs. All of the cis-acting signals necessary for termination reside within the first 13 nucleotides of the 23-nucleotide conserved gene junction. This 13-nucleotide termination s...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.11.8718-8725.1997
更新日期:1997-11-01 00:00:00
abstract::Marek's disease virus (MDV) is an alphaherpesvirus for which infection is strictly cell associated in permissive cell culture systems. In contrast to most other alphaherpesviruses, no comprehensive ultrastructural study has been published to date describing the different stages of MDV morphogenesis. To circumvent prob...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01177-07
更新日期:2007-11-01 00:00:00
abstract::Borna disease virus (BDV) is a neurotropic virus with a broad host and geographic range. Lewis rats were immunized against BDV with a recombinant vaccinia virus expressing the BDV nucleoprotein and were later infected with BDV to evaluate protection against Borna disease (BD). Relative to animals that were not immuniz...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.3.2541-2546.1999
更新日期:1999-03-01 00:00:00
abstract::The late 19S RNAs of simian virus 40 (SV40) are functionally polycistronic, i.e., all encode both VP2 and VP3. The VP3-coding sequences are situated in the same reading frame as the VP2-coding sequences, within the carboxy-terminal two-thirds of the VP2-coding sequences. To test whether VP3 is produced by proteolytic ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.3.954-961.1988
更新日期:1988-03-01 00:00:00
abstract::Previous experiments have demonstrated that adenovirus infection of human and mouse cells leads to an E1A-dependent activation of the DNA-binding capacity of a cellular transcription factor termed E2F. E2F binds to two sites in the adenovirus E2 early promoter which have been shown to be critical for E1A-dependent E2 ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.63.9.3643-3650.1989
更新日期:1989-09-01 00:00:00
abstract::Herpesvirus lytic DNA replication requires both the cis-acting element, the origin, and trans-acting factors, including virally encoded origin-binding protein, DNA replication enzymes, and auxiliary factors. Two lytic DNA replication origins (ori-Lyt) of Kaposi's sarcoma-associated herpesvirus (KSHV) have been identif...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01319-07
更新日期:2008-03-01 00:00:00
abstract::Interleukin-15 (IL-15), natural killer (NK) cells, and NK T (NKT) cells, components of the innate immune system, are known to contribute to defense against pathogens, including viruses. Here we report that IL-15(-/-) (NK(-) and NKT(-/+)) mice and RAG-2(-/-)/gamma(c)(-/-) (NK(-) and NKT(-)) mice that lack all lymphoid ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.18.10168-10171.2003
更新日期:2003-09-01 00:00:00
abstract::A gene encoding the large T antigen of polyomavirus was inserted into the baculovirus Autographa californica nuclear polyhedrosis virus so that gene expression was under the control of the strong, very late polyhedrin gene promoter. Significantly more large T antigen was produced in recombinant virus-infected insect c...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.5.1712-1716.1987
更新日期:1987-05-01 00:00:00
abstract::Mouse virus-like 30S RNAs (VL30m) constitute a family of retrotransposons, present at 100 to 200 copies, dispersed in the mouse genome. They display little sequence homology to Moloney murine leukemia virus (MoMLV), do not encode virus-like proteins, and have not been implicated in retroviral carcinogenesis. However, ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.10.8393-8402.1999
更新日期:1999-10-01 00:00:00
abstract::The three double-stranded ribonucleic acid (dsRNA) segments of the bacteriophage phi6 were isolated and shown to have similar melting temperatures and base compositions. RNA:RNA hybridization experiments with the isolated segments eliminate the possibility that the two smaller dsRNA segments arise from a cleavage of t...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.13.6.1254-1262.1974
更新日期:1974-06-01 00:00:00
abstract::The extracellular virion form (EV) of vaccinia virus (VACV) is essential for viral pathogenesis and is difficult to neutralize with antibodies. Why this is the case and how the smallpox vaccine overcomes this challenge remain incompletely understood. We previously showed that high concentrations of anti-B5 antibodies ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02152-12
更新日期:2013-02-01 00:00:00