Abstract:
:Ebola virus (EBOV) infections result in aggressive hemorrhagic fever in humans, with fatality rates reaching 90% and with no licensed specific therapeutics to treat ill patients. Advances over the past 5 years have firmly established monoclonal antibody (MAb)-based products as the most promising therapeutics for treating EBOV infections, but production is costly and quantities are limited; therefore, MAbs are not the best candidates for mass use in the case of an epidemic. To address this need, we generated EBOV-specific polyclonal F(ab')2 fragments from horses hyperimmunized with an EBOV vaccine. The F(ab')2 was found to potently neutralize West African and Central African EBOV in vitro Treatment of nonhuman primates (NHPs) with seven doses of 100 mg/kg F(ab')2 beginning 3 or 5 days postinfection (dpi) resulted in a 100% survival rate. Notably, NHPs for which treatment was initiated at 5 dpi were already highly viremic, with observable signs of EBOV disease, which demonstrated that F(ab')2 was still effective as a therapeutic agent even in symptomatic subjects. These results show that F(ab')2 should be advanced for clinical testing in preparation for future EBOV outbreaks and epidemics.IMPORTANCE EBOV is one of the deadliest viruses to humans. It has been over 40 years since EBOV was first reported, but no cure is available. Research breakthroughs over the past 5 years have shown that MAbs constitute an effective therapy for EBOV infections. However, MAbs are expensive and difficult to produce in large amounts and therefore may only play a limited role during an epidemic. A cheaper alternative is required, especially since EBOV is endemic in several third world countries with limited medical resources. Here, we used a standard protocol to produce large amounts of antiserum F(ab')2 fragments from horses vaccinated with an EBOV vaccine, and we tested the protectiveness in monkeys. We showed that F(ab')2 was effective in 100% of monkeys even after the animals were visibly ill with EBOV disease. Thus, F(ab')2 could be a very good option for large-scale treatments of patients and should be advanced to clinical testing.
journal_name
J Viroljournal_title
Journal of virologyauthors
Wang H,Wong G,Zhu W,He S,Zhao Y,Yan F,Rahim MN,Bi Y,Zhang Z,Cheng K,Jin H,Cao Z,Zheng X,Gai W,Bai J,Chen W,Zou Y,Gao Y,Gao GF,Yang S,Xia X,Qiu Xdoi
10.1128/JVI.01548-18subject
Has Abstractpub_date
2019-02-19 00:00:00issue
5eissn
0022-538Xissn
1098-5514pii
JVI.01548-18journal_volume
93pub_type
杂志文章abstract::The influenza A virus NS1 protein contains a conserved 4-amino-acid-residue PDZ-ligand binding motif (PBM) at the carboxyl terminus that can function as a virulence determinant by targeting cellular PDZ proteins. The NS1 proteins from avian and human viral isolates have consensus PBM sequences ESEV and RSKV, respectiv...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.05070-11
更新日期:2011-10-01 00:00:00
abstract::The virion RNA of Moloney murine leukemia virus (MuLV) has been translated in eukaryotic cell-free systems derived from mouse L- and human HeLa cells. In both systems at least three polypeptides, approximately 60,000, 70,000, and 180,000 in apparent molecular weight, were formed in response to the added 35S MuLV RNA. ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.18.2.627-635.1976
更新日期:1976-05-01 00:00:00
abstract:UNLABELLED:Human noroviruses are icosahedral single-stranded RNA viruses. The capsid protein is divided into shell (S) and protruding (P) domains, which are connected by a flexible hinge region. There are numerous genetically and antigenically distinct noroviruses, and the dominant strains evolve every other year. Vacc...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03176-14
更新日期:2015-03-01 00:00:00
abstract::Purified replicative form (RF) and replicative intermediate (RI) prepared from Escherichia coli cells infected with the ribonucleic acid (RNA) bacteriophage R17 were denatured with dimethyl sulfoxide at 37 C or in aqueous solvents of low ionic strength at 97 C. Denaturation was demonstrated for RF and RI by an increas...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.1.3.514-522.1967
更新日期:1967-06-01 00:00:00
abstract::HTG2 hamster cells produce a defective murine sarcoma virus lacking gp70 and, consequently, viral surface projections (knobs), but the lack of knobs appears to have no effect on intramembrane particle distribution. In addition, it has been noted that the core of the virus remains in the "immature" form as a result of ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.36.3.872-877.1980
更新日期:1980-12-01 00:00:00
abstract::Gammaherpesvirus 68 (gammaHV68, or MHV68) is a naturally occurring rodent pathogen that replicates to high titer in cell culture and is amenable to in vivo experimental evaluation of viral and host determinants of gammaherpesvirus disease. However, the inability of MHV68 to transform primary murine B cells in culture,...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02689-07
更新日期:2008-08-01 00:00:00
abstract::Phenol-extracted, infectious deoxyribonucleic acid (DNA) species from phi105 phage particles, from phi105 lysogenic bacteria, and from induced phi105 lysogenic bacteria were sedimented in sucrose gradients. Infectious DNA from phi105 particles sedimented like the bulk of mature phage DNA in neutral sucrose. Infectivit...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.5.5.604-608.1970
更新日期:1970-05-01 00:00:00
abstract:UNLABELLED:Capsid-associated tegument proteins have been identified in alpha- and betaherpesviruses to play an essential role in viral DNA packaging. Whether and how such tegument proteins exist in gammaherpesviruses have been mysteries. Here, we report a 6-Å-resolution cryo-electron microscopy (cryo-EM) structure of K...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01509-14
更新日期:2014-11-01 00:00:00
abstract::The V20 cultivar of Nicotiana tabacum was shown previously to exhibit a strain-specific restriction of long-distance movement of tobacco etch potyvirus (TEV). In V20, both TEV-HAT and TEV-Oxnard strains are capable of genome amplification and cell-to-cell movement, but only TEV-Oxnard is capable of systemic infection ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.11.8624-8631.1997
更新日期:1997-11-01 00:00:00
abstract::Type 3 reovirus inhibits L cell DNA synthesis, whereas type 1 reovirus exerts little or no effect on L cell DNA synthesis. By using recombinant viruses containing both type 1 and type 3 double-standard RNA segments, we determined that one double-stranded RNA segment, the reovirus type 3 S1 double-stranded RNA segment ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.38.1.389-392.1981
更新日期:1981-04-01 00:00:00
abstract::The genomic RNA of an alphavirus encodes four different nonstructural proteins, nsP1, nsP2, nsP3, and nsP4. The polyprotein P123 is produced when translation terminates at an opal termination codon between nsP3 and nsP4. The polyprotein P1234 is produced when translational readthrough occurs or when the opal terminati...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.80.10.4992-4997.2006
更新日期:2006-05-01 00:00:00
abstract::Previous results have indicated that Rous sarcoma virus env gene expression is specifically inhibited by antisense RNA (L.-J. Chang and C. M. Stoltzfus, Mol. Cell. Biol. 5:2341-2348, 1985). In this study, we compare the extents of inhibition by antisense RNA derived from different parts of the Rous sarcoma virus genom...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.3.921-924.1987
更新日期:1987-03-01 00:00:00
abstract:UNLABELLED:In the last decade, novel tick-borne pathogenic phleboviruses in the family Bunyaviridae, all closely related to Uukuniemi virus (UUKV), have emerged on different continents. To reproduce the tick-mammal switch in vitro, we first established a reverse genetics system to rescue UUKV with a genome close to tha...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00095-16
更新日期:2016-07-11 00:00:00
abstract::Envelope glycoprotein (Env) reactivity (ER) describes the propensity of human immunodeficiency virus type 1 (HIV-1) Env to change conformation from the metastable unliganded state in response to the binding of ligands (antibodies and soluble CD4 [sCD4]) or incubation in the cold. To investigate Env properties that fav...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01558-13
更新日期:2014-01-01 00:00:00
abstract::Transcription of the terminal protein (TP) gene of Epstein-Barr virus (EBV) in Burkitt's lymphoma cells, in EBV-negative Burkitt's lymphoma cells converted with transformation-defective (P3HR1) and transformation-competent (B95-8, AG876) EBV strains, and in EBV-immortalized cell lines was studied. A TP1 cDNA probe spa...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.1.415-423.1991
更新日期:1991-01-01 00:00:00
abstract::RNA-dependent RNA polymerases were found to be associated with two salmonid rhabdoviruses: infectious hematopoietic necrosis (IHN) virus and the virus of hemorrhagic septicemia (VHS). The protein composition of these rhabdoviruses closely resembles that of rabies virus rather than that of vesicular stomatitis virus (M...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.22.3.839-843.1977
更新日期:1977-06-01 00:00:00
abstract::Titers of vaccinia virus consistently increased in cultures of washed phytohemagglutinin-treated, peripheral blood leukocytes of a vaccinated adult. Concomitantly, a gradual rise occurred in the numbers of infected leukocytes, as determined by the infective center assay. Increase in viral titer was accompanied by cell...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.2.8.787-792.1968
更新日期:1968-08-01 00:00:00
abstract::We set out to test the hypothesis that interleukin-22 (IL-22), a cytokine crucial for epithelial cell homeostasis and recovery from tissue injury, would be protective during influenza virus infection. Recent studies have identified phenotypically and functionally unique intestinal NK cells capable of producing the cyt...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00187-10
更新日期:2010-08-01 00:00:00
abstract::Human noroviruses are the most common nonbacterial cause of gastroenteritis outbreaks, with new variants and genotypes frequently emerging. The origin of these new viruses is unknown; however, animals have been proposed as a potential source, as human noroviruses have been detected in animal species. Here, we investig...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01492-20
更新日期:2021-01-13 00:00:00
abstract::Viral infectivity factor (Vif) is required for lentivirus fitness and pathogenicity, except in equine infectious anemia virus (EIAV). Vif enhances viral infectivity by a Cullin5-Elongin B/C E3 complex to inactivate the host restriction factor APOBEC3. Core-binding factor subunit beta (CBF-β) is a cell factor that was ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01924-14
更新日期:2014-10-01 00:00:00
abstract::Seasonal influenza epidemics recur due to antigenic drift of envelope glycoprotein antigens and immune evasion of circulating viruses. Additionally, antigenic shift can lead to influenza pandemics. Thus, a universal vaccine that protects against multiple influenza virus strains could alleviate the continuing impact of...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00150-11
更新日期:2011-05-01 00:00:00
abstract::Strong determinants of the host range of influenza A viruses have been identified on the polymerase complex formed by the PB1, PB2, and PA subunits and on the nucleoprotein (NP). In the present study, molecular mechanisms that may involve these four core proteins and contribute to the restriction of avian influenza vi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00977-08
更新日期:2009-02-01 00:00:00
abstract::We previously demonstrated that the adeno-associated virus (AAV) Rep68 and Rep78 proteins are able to nick the AAV origin of DNA replication at the terminal resolution site (trs) in an ATP-dependent manner. Using four types of modified or mutant substrates, we now have investigated the substrate requirements of Rep68 ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.10.6096-6104.1993
更新日期:1993-10-01 00:00:00
abstract::The avian sarcoma and leukosis virus (ASLV) family of retroviruses contains five highly related envelope subgroups (A to E) thought to have evolved from a common viral ancestor in the chicken population. Three genetic loci in chickens determine the susceptibility or resistance of cells to infection by the subgroup A t...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02206-07
更新日期:2008-03-01 00:00:00
abstract::When ts7, a temperature-sensitive (ts) mutant of influenza B/Kanagawa/73 virus, infected MDCK cells at the nonpermissive temperature (37.5 degrees C), infectious virus was produced at very low levels compared with the yield at the permissive temperature (32 degrees C) and hemagglutinating activity and enzymatic activi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.2.1250-1254.1994
更新日期:1994-02-01 00:00:00
abstract::Temperature-sensitive (ts) mutants of the T4 phage rII gene were islated and used in temperature shift experiments that revelaed two different expressions for the normal rII (rII+) gene function in vivo: (i) an early expression (0 to 12 min postinfection at 30 C) that prevents restriction of T4 growth in Escherichia c...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.16.4.974-981.1975
更新日期:1975-10-01 00:00:00
abstract::The gastric mucosa is an important portal of entry for lymphocytic choriomeningitis virus (LCMV) infections. Within hours after intragastric (i.g.) inoculation, virus appears in the gastric epithelia, then in the mesenteric lymph nodes and spleen, and then in the liver and brain. By 72 h i.g.-inoculated virus is widel...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.11.8613-8619.1998
更新日期:1998-11-01 00:00:00
abstract::The flavivirus dengue virus (DV) infects cells through a low-pH-triggered membrane fusion reaction mediated by the viral envelope protein E. E is an elongated transmembrane protein with three domains and is organized as a homodimer on the mature virus particle. During fusion, the E protein homodimer dissociates, inser...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00170-10
更新日期:2010-06-01 00:00:00
abstract::Three mRNAs from the murine polyomavirus early region encode the three well-characterized tumor antigens. We report the existence of a fourth alternatively spliced mRNA which encodes a fourth tumor antigen, tiny T antigen, which comprises the amino-terminal domain common to all of the T antigens but is extended by six...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.8.6068-6074.1997
更新日期:1997-08-01 00:00:00
abstract::Dendritic cells (DC) are believed to play an important role in the initiation of innate and adaptive immune responses to infection, including respiratory tract infections, where respiratory DC (RDC) perform this role. In this report, we examined the susceptibilities of isolated murine RDC to influenza virus infection ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02367-07
更新日期:2008-05-01 00:00:00