Abstract:
:The pandemic threat posed by emerging zoonotic influenza A viruses necessitates development of antiviral agents effective against various antigenic subtypes. Human monoclonal antibody (hMAb) targeting the hemagglutinin (HA) stalk offers a promising approach to control influenza virus infections. Here, we investigated the ability of the hMAb 81.39a to inhibit in vitro replication of human and zoonotic viruses, representing 16 HA subtypes. The majority of viruses were effectively neutralized by 81.39a at a 50% effective concentration (EC50) of <0.01 to 4.9 μg/ml. Among group 2 HA viruses tested, a single A(H7N9) virus was not neutralized at 50 μg/ml; it contained HA2-Asp19Gly, an amino acid position previously associated with resistance to neutralization by the group 2 HA-neutralizing MAb CR8020. Notably, among group 1 HA viruses, H11-H13 and H16 subtypes were not neutralized at 50 μg/ml; they shared the substitution HA2-Asp19Asn/Ala. Conversely, H9 viruses harboring HA2-Asp19Ala were fully susceptible to neutralization. Therefore, amino acid variance at HA2-Asp19 has subtype-specific adverse effects on in vitro neutralization. Mice given a single injection (15 or 45 mg/kg of body weight) at 24 or 48 h after infection with recently emerged A(H5N2), A(H5N8), A(H6N1), or A(H7N9) viruses were protected from mortality and showed drastically reduced lung viral titers. Furthermore, 81.39a protected mice infected with A(H7N9) harboring HA2-Asp19Gly, although the antiviral effect was lessened. A(H1N1)pdm09-infected ferrets receiving a single dose (25 mg/kg) had reduced viral titers and showed less lung tissue injury, despite 24- to 72-h-delayed treatment. Taken together, this study provides experimental evidence for the therapeutic potential of 81.39a against diverse influenza A viruses. IMPORTANCE:Zoonotic influenza viruses, such as A(H5N1) and A(H7N9) subtypes, have caused severe disease and deaths in humans, raising public health concerns. Development of novel anti-influenza therapeutics with a broad spectrum of activity against various subtypes is necessary to mitigate disease severity. Here, we demonstrate that the hemagglutinin (HA) stalk-targeting human monoclonal antibody 81.39a effectively neutralized the majority of influenza A viruses tested, representing 16 HA subtypes. Furthermore, delayed treatment with 81.39a significantly suppressed virus replication in the lungs, prevented dramatic body weight loss, and increased survival rates of mice infected with A(H5Nx), A(H6N1), or A(H7N9) viruses. When tested in ferrets, delayed 81.39a treatment reduced viral titers, particularly in the lower respiratory tract, and substantially alleviated disease symptoms associated with severe A(H1N1)pdm09 influenza. Collectively, our data demonstrated the effectiveness of 81.39a against both seasonal and emerging influenza A viruses.
journal_name
J Viroljournal_title
Journal of virologyauthors
Marjuki H,Mishin VP,Chai N,Tan MW,Newton EM,Tegeris J,Erlandson K,Willis M,Jones J,Davis T,Stevens J,Gubareva LVdoi
10.1128/JVI.01284-16subject
Has Abstractpub_date
2016-11-14 00:00:00pages
10446-10458issue
23eissn
0022-538Xissn
1098-5514pii
JVI.01284-16journal_volume
90pub_type
杂志文章abstract::The entire genome of the reference strain of bluetongue virus (BTV) serotype 16 (strain RSArrrr/16) was sequenced (a total of 23,518 base pairs). The virus was obtained from the Orbivirus Reference Collection (ORC) at IAH, Pirbright, United Kingdom. The virus strain, which was previously provided by the Onderstepoort ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01672-12
更新日期:2012-09-01 00:00:00
abstract::The binding of cyclophilin A (CypA) to the human immunodeficiency virus type 1 (HIV-1) capsid protein (CA protein) is required soon after virus entry into natural target cells. In Jurkat T lymphocytes, disrupting CypA-CA interaction either by cyclosporine (Cs) treatment or by alteration (e.g., P90A) of the CA inhibits...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00682-09
更新日期:2009-11-01 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::We have purified the seven virus-specific RNAs which were previously shown to be induced in Sac(-) cells upon infection with mouse hepatitis virus strain A59 (W. J. M. Spaan, P. J. M. Rottier, M. C. Horzinek, and B. A. M. van der Zeijst, Virology 108:424-434, 1981). The individual RNAs, prepared by agarose gel electro...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.38.1.20-26.1981
更新日期:1981-04-01 00:00:00
abstract::Hepatitis C virus (HCV) replication in infected patients produces large and diverse viral populations, which give rise to drug-resistant and immune escape variants. Here, we analyzed HCV populations during transmission and diversification in longitudinal and cross-sectional samples using 454/Roche pyrosequencing, in t...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02271-09
更新日期:2010-06-01 00:00:00
abstract::Borna disease virus (BDV) is a nonsegmented negative-strand (NNS) RNA virus that is unusual because it replicates in the nucleus. The most abundant viral protein in infected cells is a 38/39-kDa doublet that is presumed to represent the nucleocapsid. Infectious particles also contain high levels of this protein, accou...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.7.5133-5139.1997
更新日期:1997-07-01 00:00:00
abstract::Live attenuated RNA viruses make highly efficient vaccines. Among them, measles virus (MV) vaccine has been given to a very large number of children and has been shown to be highly efficacious and safe. Therefore, this vaccine might be a very promising vector to immunize children against both measles and other infecti...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.21.11546-11554.2003
更新日期:2003-11-01 00:00:00
abstract::An in vitro system is described for the assembly of herpes simplex virus type 1 (HSV-1) procapsids beginning with three purified components, the major capsid protein (VP5), the triplexes (VP19C plus VP23), and a hybrid scaffolding protein. Each component was purified from insect cells expressing the relevant protein(s...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.5.4239-4250.1999
更新日期:1999-05-01 00:00:00
abstract::The v-src coding region was deleted from cloned Rous sarcoma virus DNA, and the deleted clones were tested for infectivity by transfection. All of the coding region, as well as most of the sequences lying between v-src and the unique 3' region (U3), could be deleted without affecting viability. However, at least 9 and...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.43.2.482-488.1982
更新日期:1982-08-01 00:00:00
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::The EFII cis element is a 38-bp sequence at the 5' end of the Rous sarcoma virus long terminal repeat, extending from nucleotides -229 to -192 (with respect to the viral transcription start site), which is recognized by sequence-specific DNA-binding proteins in avian fibroblast nuclear extracts (L. Sealy and R. Chalkl...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.11.6338-6352.1992
更新日期:1992-11-01 00:00:00
abstract::In the search for effective immunologic interventions to prevent and treat HIV-1 infection, standardized reference reagents are a cost-effective way to maintain robustness and reproducibility among immunological assays. To support planned and ongoing studies where clade C predominates, here we describe three virus pan...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00991-17
更新日期:2017-09-12 00:00:00
abstract::Barley stripe mosaic virus (BSMV) encodes three movement proteins in an overlapping triple gene block (TGB), but little is known about the physical interactions of these proteins. We have characterized a ribonucleoprotein (RNP) complex consisting of the TGB1 protein and plus-sense BSMV RNAs from infected barley plants...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02586-07
更新日期:2008-05-01 00:00:00
abstract::We describe the use of herpesvirus promoters to regulate the expression of a Sindbis virus replicon (SINrep/LacZ). We isolated cell lines that contain the cDNA of SINrep/LacZ under the control of a promoter from a herpesvirus early gene which requires regulatory proteins encoded by immediate-early genes for expression...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.3.1998-2005.1999
更新日期:1999-03-01 00:00:00
abstract::The organization of adeno-associated virus serotype 4 (AAV 4) DNA was probed by using restriction enzymes. The cleavage sites of the following enzymes were mapped: BglII, BamI, HincII, KpnI, PstI, SalI, SstI, and XhoI. The orientation of transcription on the physical cleavage map was determined by locating the fragmen...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.35.3.653-661.1980
更新日期:1980-09-01 00:00:00
abstract::The VP24 protein plays an essential, albeit poorly understood role in the filovirus life cycle. VP24 is only 30% identical between Marburg virus and the ebolaviruses. Furthermore, VP24 from the ebolaviruses is immunosuppressive, while that of Marburg virus is not. The crystal structure of Marburg virus VP24, presented...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03565-13
更新日期:2014-05-01 00:00:00
abstract::Human cytomegalovirus (HCMV) has emerged as a clinically opportunistic pathogen that targets multiple types of ocular cells and tissues, including the iris region of the uveal tract during anterior uveitis. In this report, we used primary cultures of human iris stroma (HIS) cells derived from human eye donors to inves...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00109-15
更新日期:2015-05-01 00:00:00
abstract::Identifying protease cleavage sites contributes to our understanding of their specificity and biochemical properties and can help in designing specific inhibitors. One route to this end is the generation and screening of random libraries of cleavage sites. Both synthetic and phage-displayed libraries have been extensi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.22.10563-10570.2000
更新日期:2000-11-01 00:00:00
abstract::The deoxyribonucleic acid (DNA) of Escherichia coli B is converted by colicin E2 to products soluble in cold trichloroacetic acid; we show that this DNA degradation (hereafter termed solubilization) is subject to inhibition by infection with bacteriophage T4. At least two modes of inhibition may be differentiated on t...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.8.3.303-310.1971
更新日期:1971-09-01 00:00:00
abstract::The genomic RNA 3' noncoding region is believed to be a major cis-acting molecular genetic determinant for regulating picornavirus negative-strand RNA synthesis by promoting replication complex recognition. We report the replication of two picornavirus RNAs harboring complete deletions of the genomic RNA 3' noncoding ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.11.8868-8874.1997
更新日期:1997-11-01 00:00:00
abstract::The cellular tropism of the feline immunodeficiency virus (FIV) is affected by changes in variable region 3 (V3) of the surface (SU) envelope glycoprotein (Verschoor, E. J., et al., J. Virol. 69:4752-4757, 1995). By using high-dose DNA transfection, an FIV molecular clone with a non-CRFK-tropic V3 acquired the ability...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.9.7132-7135.1997
更新日期:1997-09-01 00:00:00
abstract::The ability of the 3A protein of coxsackievirus B (CVB) to inhibit protein secretion was investigated for this study. Here we show that the ectopic expression of CVB 3A blocked the transport of both the glycoprotein of vesicular stomatitis virus, a membrane-bound secretory marker, and the alpha-1 protease inhibitor, a...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.8.5163-5173.2005
更新日期:2005-04-01 00:00:00
abstract::Goat and rabbit antisera prepared against a purified Rauscher murine leukemia virus glycoprotein (gp69/71) rapidly neutralized spleen focus-forming virus in Rauscher and Friend virus preparations. Absorption studies revealed that most of the neutralizing activity of goat anti-Rauscher virus gp69/71 serum was directed ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.14.1.187-189.1974
更新日期:1974-07-01 00:00:00
abstract::We generated a recombinant influenza A virus (Mmut) that produced low levels of matrix (M1) and M2 proteins in infected cells. Mmut virus propagated to significantly lower titers than did wild-type virus in cells infected at low multiplicity. By contrast, virion morphology and incorporation of viral proteins and vRNAs...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.12.7926-7932.2005
更新日期:2005-06-01 00:00:00
abstract::Chemokines induce the directional migration of targeted populations of leukocytes during periods of inflammation. Moreover, these molecules also regulate T-cell activation and differentiation following antigenic stimulation. In the present study, the contributions of the CC chemokine ligand 3 (CCL3) to the differentia...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.7.4004-4014.2003
更新日期:2003-04-01 00:00:00
abstract::Purified avian myeloblastosis virus was iodinated by the lactoperoxidase method. Disruption of the labeled virions and chromatography of the viral proteins showed that radioiodine was associated only with the glycoproteins of the viral envelope. Reaction of the radiolabeled virus with antiviral antibody followed by mi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.13.1.42-45.1974
更新日期:1974-01-01 00:00:00
abstract::The human papillomavirus (HPV) E6 oncoproteins recruit the cellular ubiquitin ligase E6AP/UBE3A to target cellular substrates for proteasome-mediated degradation, and one consequence of this activity is the E6 stimulation of E6AP autoubiquitination and degradation. Recent studies identified an autism-linked mutation w...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01390-17
更新日期:2017-10-27 00:00:00
abstract::Waterfowl are the natural reservoir of all influenza A viruses, which are usually nonpathogenic in wild aquatic birds. However, in late 2002, outbreaks of highly pathogenic H5N1 influenza virus caused deaths among wild migratory birds and resident waterfowl, including ducks, in two Hong Kong parks. In February 2003, a...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.78.9.4892-4901.2004
更新日期:2004-05-01 00:00:00
abstract::Highly pathogenic H5N1 influenza A virus remains a substantial threat to public health. To understand the molecular basis and host mechanism for the high virulence of H5N1 viruses in mammals, we compared two H5N1 isolates which have similar genetic backgrounds but greatly differ in their virulence in mice. A/Chicken/J...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02891-12
更新日期:2013-03-01 00:00:00
abstract::Using a recently developed model for in vitro generation of pp65-positive polymorphonuclear leukocytes (PMNLs), we demonstrated that PMNLs from immunocompetent subjects may harbor both infectious human cytomegalovirus (HCMV) and viral products (pp65, p72, DNA, and immediate-early [IE] and pp67 late mRNAs) as early as ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.12.5629-5638.2000
更新日期:2000-06-01 00:00:00