Publications

enzootic nasal tumor virus envelope requires a very acidic ph for fusion activation and infection.	enzootic nasal tumor virus (entv) is a close relative of jaagsiekte sheep retrovirus (jsrv), and the two viruses use the same receptor, hyaluronidase 2 (hyal2), for cell entry. we report here that, unlike the jsrv envelope (env) protein, the entv env protein does not induce cell fusion at phs of 5.0 and above but requires a much lower ph (4.0 to 4.5) for fusion to occur. the entry of entv env pseudovirions was substantially inhibited by bafilomycin a1 (bafa1) but was surprisingly enhanced by lys ...	2008	18632865
establishment of a lacz marker rescue assay to detect infectious rd114 virus.	cats have an infectious endogenous retrovirus, named rd114 virus, and there is a possibility that rd114 virus has contaminated live attenuated vaccines, for which feline cells are used as a substrate. to monitor infectious rd114 virus in vaccines for cats, we developed a lacz marker rescue assay to detect infectious rd114 virus. among four human cell lines examined, te671 cells (human rhabdomyosarcoma) were most susceptible to rd114 virus and supported rd114 replication efficiently. infection wa ...	2008	18772552
mouse apobec3 restricts friend leukemia virus infection and pathogenesis in vivo.	several members of the apolipoprotein b mrna-editing enzyme catalytic polypeptide-like complex 3 (apobec3) family in primates act as potent inhibitors of retroviral replication. however, lentiviruses have evolved mechanisms to specifically evade host apobec3. likewise, murine leukemia viruses (mulv) exclude mouse apobec3 from the virions and cleave virion-incorporated apobec3. although the betaretrovirus mouse mammary tumor virus has been shown to be susceptible to mouse apobec3, it is not known ...	2008	18786991
identification of postentry restrictions to mason-pfizer monkey virus infection in new world monkey cells.	trim5alpha has been shown to be a major postentry determinant of the host range for gammaretroviruses and lentiviruses and, more recently, spumaviruses. however, the restrictive potential of trim5alpha against other retroviruses has been largely unexplored. we sought to determine whether or not mason-pfizer monkey virus (m-pmv), a prototype betaretrovirus isolated from rhesus macaques, was sensitive to restriction by trim5alpha. cell lines from both old world and new world primate species were s ...	2008	18799582
coevolution of endogenous betaretroviruses of sheep and their host.	sheep betaretroviruses offer a unique model system to study the complex interaction between retroviruses and their host. jaagsiekte sheep retrovirus (jsrv) is a pathogenic exogenous retrovirus and the causative agent of ovine pulmonary adenocarcinoma. the sheep genome contains at least 27 copies of endogenous retroviruses (enjsrvs) highly related to jsrv. enjsrvs have played several roles in the evolution of the domestic sheep as they are able to block the jsrv replication cycle and play a criti ...	2008	18818869
structure of the capsid amino-terminal domain from the betaretrovirus, jaagsiekte sheep retrovirus.	jaagsiekte sheep retrovirus is a betaretrovirus and the causative agent of pulmonary adenocarcinoma, a transmissible lung tumour of sheep. here we report the crystal structure of the capsid amino-terminal domain and examine the self-association properties of jaagsiekte sheep retrovirus capsid. we find that the structure is remarkably similar to the amino-terminal domain of the alpharetrovirus, avian leukosis virus, revealing a previously undetected evolutionary similarity. examination of capsid ...	2009	19007792
broad-spectrum inhibition of retroviral and filoviral particle release by tetherin.	the expression of many putative antiviral genes is upregulated when cells encounter type i interferon (ifn), but the actual mechanisms by which many ifn-induced gene products inhibit virus replication are poorly understood. a recently identified ifn-induced antiretroviral protein, termed tetherin (previously known as bst-2 or cd317), blocks the release of nascent human immunodeficiency virus type 1 (hiv-1) particles from infected cells, and an hiv-1 accessory protein, vpu, acts as a viral antago ...	2009	19036818
premature processing of mouse mammary tumor virus gag polyprotein impairs intracellular capsid assembly.	mouse mammary tumor virus (mmtv) is the prototypical member of the betaretrovirus genus, but the processes of its morphogenesis are poorly characterized. in this report, we describe an unusual intracellular processing of mmtv gag polyprotein in human 293t cells transiently expressing mmtv from heterologous promoter. the same specific cleavage products of the viral protease were seen for the wild type as well as for nonmyristylated mutant of mmtv gag polyprotein completely defective in the partic ...	2009	19046754
nmr structure of the n-terminal domain of capsid protein from the mason-pfizer monkey virus.	the high-resolution structure of the n-terminal domain (ntd) of the retroviral capsid protein (ca) of mason-pfizer monkey virus (m-pmv), a member of the betaretrovirus family, has been determined by nmr. the m-pmv ntd ca structure is similar to the other retroviral capsid structures and is characterized by a six alpha-helix bundle and an n-terminal beta-hairpin, stabilized by an interaction of highly conserved residues, pro1 and asp57. since the role of the beta-hairpin has been shown to be crit ...	2009	19527730
development of a generic real-time pcr assay for simultaneous detection of proviral dna of simian betaretrovirus serotypes 1, 2, 3, 4 and 5 and secondary uniplex assays for specific serotype identification.	simian betaretroviruses (formerly type d retroviruses; srv) are a group of closely related retroviruses for which the natural host species are asian monkeys of the genus macaca. five serotypes have been identified by classical neutralization assays and three additional untyped variants have been reported (srv(tsukuba), srv-6, srv-7). these viruses may be significant pathogens in macaque colonies, causing a broad spectrum of clinical disease secondary to viral-induced immune suppression. undetect ...	2009	19664660
conformational changes of the n-terminal part of mason-pfizer monkey virus p12 protein during multimerization.	the mason-pfizer monkey virus is a prototype betaretrovirus with the defining characteristic that it assembles spherical immature particles from gag-related polyprotein precursors within the cytoplasm of the infected cell. it was shown previously that the n-terminal part of the gag p12 domain (wt-np12) is required for efficient assembly. however, the precise role for p12 in mediating gag-gag interaction is still poorly understood. in this study we employed detailed circular dichroism spectroscop ...	2009	19699504
unintended spread of a biosafety level 2 recombinant retrovirus.	contamination of vertebrate cell lines with animal retroviruses has been documented repeatedly before. although such viral contaminants can be easily identified with high sensitivity by pcr, it is impossible to screen for all potential contaminants. therefore, we explored two novel methods to identify viral contaminations in cell lines without prior knowledge of the kind of contaminant.	2009	19772602
jaagsiekte sheep retrovirus encodes a regulatory factor, rej, required for synthesis of gag protein.	retroviruses express gag and pol proteins by translation of unspliced genome-length viral rna. for some retroviruses, transport of unspliced viral rna to the cytoplasm is mediated by small regulatory proteins such as human immunodeficiency virus rev, while other retroviruses contain constitutive transport elements in their rnas that allow transport without splicing. in this study, we found that the betaretrovirus jaagsiekte sheep retrovirus (jsrv) encodes within the env gene a trans-acting facto ...	2009	19776124
identification and mutational analysis of a rej response element in jaagsiekte sheep retrovirus rna.	jaagsiekte sheep retrovirus (jsrv) is a simple betaretrovirus causing a contagious lung cancer of sheep. jsrv encodes unspliced and spliced viral rnas, among which unspliced rna encodes gag and pol proteins and a singly spliced mrna encodes env protein. in another study we found that jsrv encodes a regulatory protein, rej, that is responsible for synthesis of gag polyprotein from unspliced viral rna. rej is encoded in the 5' end of env, and it enhances nuclear export or accumulation of cytoplasm ...	2009	19776134
detection of human mammary tumor virus proteins in human breast cancer cells.	mouse mammary tumor virus (mmtv) has been proven to induce mammary cancer in mice. mmtv-like env gene sequences have been detected in one-third of the human breast tumors studied. the whole proviral structure with 95% homology to mmtv was found in two human breast tumors and was designated as human mammary tumor virus (hmtv). hmtv viral particles with betaretroviral features have been isolated. in addition, a retrovirus called human betaretrovirus (hbrv), homologous to the mentioned retroviruses ...	2010	19781575
simian betaretrovirus infection in a colony of cynomolgus monkeys (macaca fascicularis).	of the 419 laboratory-bred cynomolgus macaques (macaca fascicularis) in a breeding colony at our institution, 397 (95%) exhibited antibodies or viral rna (or both) specific for simian betaretrovirus (srv) in plasma. pregnant monkeys (n= 95) and their offspring were tested to evaluate maternal-infant infection with srv. at parturition, the first group of pregnant monkeys (n = 76) was antibody-positive but rna-negative, the second group (n = 14 monkeys) was positive for both antibody and rna, and ...	2010	20158949
full-length genome sequence analysis of enzootic nasal tumor virus reveals an unusually high degree of genetic stability.	enzootic nasal tumor virus (entv) is a betaretrovirus of sheep (entv-1) and goats (entv-2) associated with neoplastic transformation of epithelial cells of the ethmoid turbinate. confirmation of the role of entv in the pathogenesis of enzootic nasal adenocarcinoma (ena) has yet to be resolved due to the lack of an infectious molecular clone and the inability to culture the virus. very little is known about the prevalence of this disease, particularly in north america, and only one full-length se ...	2010	20398709
an updated review of simian betaretrovirus (srv) in macaque hosts.	this review is an updated summary of nearly 30 years of srv history and provides new and critical findings of original research accomplished in the last 5 years including, but not limited to, the pathogenetic mechanisms underlying the origin of hematopoietic abnormalities observed in infected hosts and proposed new srv serotypes. despite major advances in the understanding and control of srv disease, much more remains to be learned and srv continues to be an exciting and attractive primate model ...	2010	20412379
cyclosporine a inhibits in vitro replication of betaretrovirus associated with primary biliary cirrhosis.	up to one-third of patients with primary biliary cirrhosis (pbc) experience recurrent disease following liver transplantation, which is associated with earlier and more severe recurrence in patients treated with tacrolimus as compared with cyclosporine a (csa). as the latter has known antiviral activity, we hypothesized that csa has the ability to inhibit the betaretrovirus characterized from patients with pbc.	2010	20492501
human mammary tumor virus in inflammatory breast cancer.	the authors have found that retroviral sequences with 85% to 95% homology to the mouse mammary tumor virus were present in 40% of the sporadic breast cancers of american women. these sequences were not found in normal breasts or other tumors. a whole proviral structure was detected in 2 tumors. breast cancer cells in culture were shown to contain and shed betaretroviral particles. this virus was designated human mammary tumor virus (hmtv). the authors have investigated the presence of hmtv seque ...	2010	20503403
increases in iga(+) b cells in peyer's patches during milk-borne mouse mammary tumor virus infection are influenced by toll-like receptor 4 and are completely dependent on the superantigen response.	mouse mammary tumor virus (mmtv) is a milk-borne betaretrovirus that has developed strategies to exploit and subvert the host immune system. although mammary glands are the final target of infection, peyer's patches (pp) are the entry site of the virus. herein, we show that the infection induces increases in the number of pp iga(+) b cells and higher expression of the α circular transcript, which is a specific marker of the switch to iga. in addition, iga(+) b-cell increases correlated with high ...	2010	20685932
absence of markers of betaretrovirus infection in human pulmonary adenocarcinoma.	a proportion of human pulmonary adenocarcinomas has been shown previously to express an antigen related to the gag protein of a betaretrovirus, jaagsiekte sheep retrovirus, that causes ovine pulmonary adenocarcinoma. to investigate further the hypothesis that a retrovirus might be present in human lung adenocarcinoma, we examined specimens from patients with lung cancer for evidence of retroviral infection by immunohistochemistry, reverse transcriptase-polymerase chain reaction, immunoblotting a ...	2010	20825971
identification of novel endogenous betaretroviruses which are transcribed in the bovine placenta.	sequences of retroviral origin occupy approximately 10% of mammalian genomes. various infectious endogenous retroviruses (ervs) and functional retroviral elements have been reported for several mammals but not cattle. here, we identified two proviruses, designated bovine endogenous retrovirus k1 (berv-k1) and berv-k2, containing full-length envelope (env) genes in the bovine genome. phylogenetic analysis revealed that they belong to the genus betaretrovirus. by reverse transcription (rt)-pcr, bo ...	2010	21084469
anti-infective activities of pelargonium sidoides (eps® 7630): effects of induced no production on leishmania major in infected macrophages and antiviral effects as assessed in a fibroblast-virus protection assay.	eps® 7630 is an aqueous-ethanolic extract of the roots of pelargonium sidoides, employed in the treatment of upper respiratory tract infections. its anti-infective activity is supposed to be associated with the activation of the nonspecific immune system. using leishmania major gfp-infected murine bmmφ, the no production of eps® 7630-activated macrophages was correlated with the reduction of the gfp signal measured at single cell levels using flow cytometry. the anti-infectious effect of eps® 76 ...	2010	21104606
the evidence supports a viral aetiology for primary biliary cirrhosis.		2010	21147183
killing two birds with one stone.		2011	21195252
differential sensitivities of retroviruses to integrase strand transfer inhibitors.	integrase inhibitors are emerging anti-human immunodeficiency virus (hiv) drugs, and multiple retroviruses and transposable elements were evaluated here for susceptibilities to raltegravir (ral) and elvitegravir (evg). all viruses, including primate and nonprimate lentiviruses, a betaretrovirus, a gammaretrovirus, and the alpharetrovirus rous sarcoma virus (rsv), were susceptible to inhibition by ral. evg potently inhibited all lentiviruses and intermediately inhibited betaretrovirus and gammare ...	2011	21270168
mouse mammary tumor virus in anti-mitochondrial antibody producing mouse models.	a human betaretrovirus resembling the mouse mammary tumor virus (mmtv) has been characterized in primary biliary cirrhosis (pbc) and associated with aberrant pyruvate dehydrogenase complex (pdc)-e2-like expression. as mmtv is prevalent in mice as either an exogenous or endogenous infection, we tested the hypothesis that mmtv is linked with anti-mitochondrial antibody (ama) production in models with severe immune dysfunction.	2011	21334408
chemical induction of endogenous retrovirus particles from the vero cell line of african green monkeys.	endogenous retroviral sequences are present in high copy number in the genomes of all species and may be expressed as rnas, however, the majority are defective for virus production. although virus has been isolated from various old world monkey and new world monkey species, there has been no report of endogenous retroviruses produced from african green monkey (agm) tissues or cell lines. we have recently developed a step-wise approach for evaluating the presence of latent viruses by chemical ind ...	2011	21543506
the signal peptide of a recently integrated endogenous sheep betaretrovirus envelope plays a major role in eluding gag-mediated late restriction.	the exogenous and pathogenic jaagsiekte sheep retrovirus (jsrv) co-exists with highly related and biologically active endogenous retroviruses (enjsrvs). the endogenous enjs56a1 locus possesses a defective gag polyprotein which blocks the late replication steps of related exogenous and endogenous retroviruses by a mechanism known as jsrv late restriction (jlr). conversely, enjsrv-26, which most likely integrated into the sheep genome less than 200 years ago, is able to escape jlr. in this study, ...	2011	21593182
ensuring the safety of vaccine cell substrates by massively parallel sequencing of the transcriptome.	massively parallel, deep, sequencing of the transcriptome coupled with algorithmic analysis to identify adventitious agents (mp-seq™) is an important adjunct in ensuring the safety of cells used in vaccine production. such cells may harbour novel viruses whose sequences are unknown or latent viruses that are only expressed following stress to the cells. mp-seq is an unbiased and comprehensive method to identify such viruses and other adventitious agents without prior knowledge of the nature of t ...	2011	21651935
clathrin facilitates the morphogenesis of retrovirus particles.	the morphogenesis of retroviral particles is driven by gag and gagpol proteins that provide the major structural component and enzymatic activities required for particle assembly and maturation. in addition, a number of cellular proteins are found in retrovirus particles; some of these are important for viral replication, but many lack a known functional role. one such protein is clathrin, which is assumed to be passively incorporated into virions due to its abundance at the plasma membrane. we ...	2011	21738476
[regulatory t cell depletion increases the number of cd8 cells during mouse mammary tumor virus infection.]	mouse mammary tumor virus (mmtv) is a milk-borne betaretrovirus that has developed strategies to exploit and subvert the host immune system. we have shown in a natural model of mmtv infection that the virus causes early and progressive increases in superantigen (sag)-specific cd4+ cd25+ foxp3+ regulatory t cells (treg) in peyer's patches. herein, we evaluated whether the depletion of treg cells affects the cd8+ population during milk-borne mmtv infection. at day 6 of infection, the depletion of ...	2011	21745773
simultaneous detection of antibodies to five simian viruses in nonhuman primates using recombinant viral protein based multiplex microbead immunoassays.	routine screening for infectious agents is critical in establishing and maintaining specific pathogen free (spf) nonhuman primate (nhp) colonies. more efficient, higher throughput, less costly reagent, and reduced sample consumption multiplex microbead immunoassays (mmias) using purified viral lysates have been developed previously to address some disadvantages of the traditional individual enzyme-linked immunosorbent assay (elisa) methods. to overcome some of the technical and biosafety difficu ...	2011	21945221
PBC: Animal Models of Cholangiopathies and Possible Endogenous Viral Infections.	Primary Biliary Cirrhosis (PBC) is considered an autoimmune disease characterized by immune-mediated destruction of the intrahepatic bile ducts and its characteristic serologic marker, the anti-mitochondrial antibody (AMA). Several factors were proposed to clarify the pathological and immunological mechanisms of PBC. Immunological reaction with a bacterial or a viral association was identified in the previous report, and it seems probable that PBC was thought to have such an etiology. The majori ...	2012	22007316
single residues in the surface subunits of oncogenic sheep retrovirus envelopes distinguish receptor-mediated triggering for fusion at low ph and infection.	jaagsiekte sheep retrovirus (jsrv) and enzootic nasal tumor virus (entv) are two closely related oncogenic retroviruses that share the same cellular receptor yet exhibit distinct fusogenicity and infectivity. here, we find that the low fusogenicity of entv envelope protein (env) is not because of receptor binding, but lies in its intrinsic insensitivity to receptor-mediated triggering for fusion at low ph. distinct from jsrv, shedding of entv surface (su) subunit into culture medium was not enha ...	2011	22018783
Identification, characterization, and comparative genomic distribution of the HERV-K (HML-2) group of human endogenous retroviruses.	ABSTRACT:	2011	22067224
The 5' Leader Sequence of Mouse Mammary Tumor Virus Enhances Expression of the Envelope and Reporter Genes.	Mouse mammary tumor virus (MMTV) is a complex betaretrovirus, which utilizes a Rev-like auxiliary protein Rem to export the unspliced viral RNA from the nucleus. MMTV env mRNA appears to be exported via a distinct, Rem-independent, mechanism. Here, we analyzed the effect of an extensively folded region coinciding with the 5' leader sequence on env gene expression. We found that the presence of the 5' leader stimulates expression of the envelope protein. Enhanced Env production was accompanied b ...	2011	22113011