| interferon alfacon-1 protects hamsters from lethal pichinde virus infection. | hemorrhagic fever of arenaviral origin is a frequently fatal infectious disease of considerable priority to the biodefense mission. historically, the treatment of arenaviral infections with alpha interferons has not yielded favorable results. here we present evidence that interferon alfacon-1, a nonnaturally occurring bioengineered alpha interferon approved for the treatment of chronic hepatitis c, is active against pichinde and tacaribe arenaviruses in cell culture. in the hamster model of pich ... | 2005 | 15917537 |
| narrowed tcr repertoire and viral escape as a consequence of heterologous immunity. | why some virus-specific cd8 tcr repertoires are diverse and others restricted or "oligoclonal" has been unknown. we show here that oligoclonality and extreme clonal dominance can be a consequence of t cell cross-reactivity. lymphocytic choriomeningitis virus (lcmv) and pichinde virus (pv) encode np(205-212) epitopes that induce different but highly cross-reactive diverse tcr repertoires. homologous viral challenge of immune mice only slightly skewed the repertoire and enriched for predictable tc ... | 2006 | 16614754 |
| differential signaling networks induced by mild and lethal hemorrhagic fever virus infections. | the family arenaviridae includes several national institutes of allergy and infections diseases category a select agents which cause hemorrhagic fever. there are few vaccines available, and treatment is limited to ribavirin, which varies in efficacy. development of new antiviral compounds has been hindered by a lack of understanding of the molecular basis of pathogenesis. we used two variants of pichinde virus, one attenuated and one virulent in the guinea pig model, to delineate the host determ ... | 2006 | 17005702 |
| combinatorial ribavirin and interferon alfacon-1 therapy of acute arenaviral disease in hamsters. | several arenaviruses endemic to south america (junin, machupo, and guanarito) and africa (lassa) are known to cause frequently fatal haemorrhagic fever. with the exception of ribavirin, which has demonstrated efficacy in cases of lassa fever, there is no other effective therapeutic for the treatment of arenaviral haemorrhagic fever. we have recently reported that consensus interferon-a (ifn alfacon-1) can protect hamsters from lethal pichinde virus (pcv) infection, which serves as a model for ac ... | 2006 | 17066896 |
| identification of differentially activated cell-signaling networks associated with pichinde virus pathogenesis by using systems kinomics. | phosphorylation plays a key role in regulating many signaling pathways. although studies investigating the phosphorylated forms of signaling pathways are now commonplace, global analysis of protein phosphorylation and kinase activity has lagged behind genomics and proteomics. we have used a kinomics approach to study the effect of virus infection on host cell signaling in infected guinea pigs. delineating the host responses which lead to clearance of a pathogen requires the use of a matched, com ... | 2007 | 17151108 |
| inhibition of arenavirus infection by a glycoprotein-derived peptide with a novel mechanism. | the family arenaviridae includes a number of viruses of public health importance, such as the category a hemorrhagic fever viruses lassa virus, junin virus, machupo virus, guanarito virus, and sabia virus. current chemotherapy for arenavirus infection is limited to the nucleoside analogue ribavirin, which is characterized by considerable toxicity and treatment failure. using pichinde virus as a model arenavirus, we attempted to design glycoprotein-derived fusion inhibitors similar to the fda-app ... | 2014 | 24850726 |
| thioaptamer decoy targeting of ap-1 proteins influences cytokine expression and the outcome of arenavirus infections. | viral haemorrhagic fever (vhf) is caused by a number of viruses, including arenaviruses. the pathogenesis is believed to involve dysregulation of cytokine production. the arenaviruses lassa virus and pichinde virus have a tropism for macrophages and other reticuloendothelial cells and both appear to suppress the normal macrophage response to virus infection. a decoy thioaptamer, xby-s2, was developed and was found to bind to ap-1 transcription factor proteins. the p388d1 macrophage-like cell lin ... | 2007 | 17325372 |
| in vitro and in vivo activities of t-705 against arenavirus and bunyavirus infections. | there is a need for the development of effective antivirals for the treatment of severe viral diseases caused by members of the virus families bunyaviridae and arenaviridae. the pyrazine derivative t-705 (6-fluoro-3-hydroxy-2-pyrazinecarboxamide) has demonstrated remarkable antiviral activity against influenza virus and, to a lesser degree, against some other rna viruses (y. furuta, k. takahashi, y. fukuda, m. kuno, t. kamiyama, k. kozaki, n. nomura, h. egawa, s. minami, y. watanabe, h. narita, ... | 2007 | 17606691 |
| arenavirus entry occurs through a cholesterol-dependent, non-caveolar, clathrin-mediated endocytic mechanism. | arenaviruses are important causes of viral hemorrhagic fevers in humans. arenavirus infection of cells occurs via a ph-dependent endocytic route, but detailed studies of entry pathways have not been done. we investigated the role of cell membrane cholesterol, caveolae, and clathrin coated pits in infection by lassa virus (lasv), which utilizes alpha-dystroglycan (alpha-dg) as a receptor, and pichindé virus (picv), which does not. depletion of cellular cholesterol by treatment with methyl betacyc ... | 2007 | 17698159 |
| rt-pcr assay for detection of lassa virus and related old world arenaviruses targeting the l gene. | this study describes an rt-pcr assay targeting the l rna segment of arenaviruses. conserved regions were identified in the polymerase domain of the l gene on the basis of published sequences for lassa virus, lymphocytic choriomeningitis virus (lcmv), pichinde virus and tacaribe virus, as well as 15 novel sequences for lassa virus, lcmv, ippy virus, mobala virus and mopeia virus determined in this study. using these regions as target sites, a pcr assay for detection of all known old world arenavi ... | 2007 | 17905372 |
| dehydroepiandrosterone, epiandrosterone and synthetic derivatives inhibit junin virus replication in vitro. | in the present paper the in vitro antiviral activity of dehydroepiandrosterone (dhea), epiandrosterone (ea) and 16 synthetic derivatives against junin virus (junv) replication in vero cells was studied. dhea and ea caused a selective inhibition of the replication of junv and other members of the arenaviridae family such as pichinde virus and tacaribe virus. the compounds were not virucidal to cell-free junv. the impairment of viral replication was not due to an inhibitory effect of the steroids ... | 2008 | 18462821 |
| genome comparison of virulent and avirulent strains of the pichinde arenavirus. | a virulent (p18) strain of the pichinde arenavirus produces a disease in guinea pigs that somewhat mimics human lassa fever, whereas an avirulent (p2) strain of this virus is attenuated in infected animals. it has been speculated that the composition of viral genomes may confer the degree of virulence in an infected host; the complete sequence of the viral genomes, however, is not known. here, we provide for the first time genomic sequences of the s and l segments for both the p2 and p18 strains ... | 2008 | 18506572 |
| cytokine patterns in a comparative model of arenavirus haemorrhagic fever in guinea pigs. | arenaviruses such as lassa virus cause a spectrum of disease in humans ranging from mild febrile illness to lethal haemorrhagic fever. the contributions of innate immunity to protection or pathogenicity are unknown. we compared patterns of expression of cytokines of innate immunity in mild versus severe arenavirus disease using an established guinea pig model based on the macrophage-tropic arenavirus pichinde virus (picv). cytokine transcripts were measured by using real-time rt-pcr in target or ... | 2008 | 18796726 |
| targeting inside-out phosphatidylserine as a therapeutic strategy for viral diseases. | there is a pressing need for antiviral agents that are effective against multiple classes of viruses. broad specificity might be achieved by targeting phospholipids that are widely expressed on infected host cells or viral envelopes. we reasoned that events occurring during virus replication (for example, cell activation or preapoptotic changes) would trigger the exposure of normally intracellular anionic phospholipids on the outer surface of virus-infected cells. a chimeric antibody, bavituxima ... | 2008 | 19029986 |
| molecular determinants of pichinde virus infection of guinea pigs--a small animal model system for arenaviral hemorrhagic fevers. | arenaviruses are enveloped single-strand rna viruses that mostly have natural hosts in rodents. upon infection of humans, several arenaviruses can cause severe hemorrhagic fever diseases, including lassa fever that is endemic in west africa. the virulence mechanism of these deadly arenaviruses can be studied in a safe and economical small animal model-guinea pigs infected by a nonpathogenic arenavirus pichinde virus (picv), a virulent strain of which can cause similar disease syndromes in guinea ... | 2009 | 19751405 |
| pichinde virus induces microvascular endothelial cell permeability through the production of nitric oxide. | this report is the first to demonstrate infection of human endothelial cells by pichinde virus (pic). pic infection induces an upregulation of the inducible nitric oxide synthase gene; as well as an increase in detectable nitric oxide (no). pic induces an increase in permeability in endothelial cell monolayers which can be abrogated at all measured timepoints with the addition of a nitric oxide synthase inhibitor, indicating a role for no in the alteration of endothelial barrier function. becaus ... | 2009 | 19814828 |
| efficacy of favipiravir (t-705) and t-1106 pyrazine derivatives in phlebovirus disease models. | several studies have reported favipiravir (t-705) to be effective in treating a number of viral diseases modeled in rodent systems. notably, the related pyrazine derivative, t-1106, was found to be more effective than t-705 in treating yellow fever virus infection in hamsters. based on these findings, we hypothesized that t-1106 may be more effective in treating hepatotropic punta toro virus (ptv, phlebovirus) infection in rodents. in cell culture, the inhibitory concentrations of the compounds ... | 2010 | 19874853 |
| attenuated and lethal variants of pichindé virus induce differential patterns of nf-kappab activation suggesting a potential target for novel therapeutics. | lassa virus pathogenesis is believed to involve dysregulation of cytokines. we have previously shown nuclear factor-kappab (nf-kappab) inhibition using a bsl-2 model for lassa fever. here we further define the potential mechanism for nf-kappab inhibition as involving increased levels of repressive p50/p50 homodimers, and suggest a novel therapeutic strategy that acts via modulation of host signaling. | 2009 | 19951183 |
| cd8 t cell cross-reactivity networks mediate heterologous immunity in human ebv and murine vaccinia virus infections. | in this study, we demonstrate complex networks of cd8 t cell cross-reactivities between influenza a virus and ebv in humans and between lymphocytic choriomeningitis virus and vaccinia virus in mice. we also show directly that cross-reactive t cells mediate protective heterologous immunity in mice. subsets of t cell populations reactive with one epitope cross-reacted with either of several other epitopes encoded by the same or the heterologous virus. human t cells specific to ebv-encoded bmlf1(28 ... | 2010 | 20164414 |
| proteomic analysis of pichindé virus infection identifies differential expression of prothymosin-alpha. | the arenaviruses include a number of important pathogens including lassa virus and junin virus. presently, the only treatment is supportive care and the antiviral ribavirin. in the event of an epidemic, patient triage may be required to more effectively manage resources; the development of prognostic biomarker signatures, correlating with disease severity, would allow rational triage. using a pair of arenaviruses, which cause mild or severe disease, we analyzed extracts from infected cells using ... | 2010 | 20706531 |
| assessing changes in vascular permeability in a hamster model of viral hemorrhagic fever. | a number of rna viruses cause viral hemorrhagic fever (vhf), in which proinflammatory mediators released from infected cells induce increased permeability of the endothelial lining of blood vessels, leading to loss of plasma volume, hypotension, multi-organ failure, shock and death. the optimal treatment of vhf should therefore include both the use of antiviral drugs to inhibit viral replication and measures to prevent or correct changes in vascular function. although rodent models have been use ... | 2010 | 20846417 |
| t-705 (favipiravir) inhibition of arenavirus replication in cell culture. | a number of new world arenaviruses (junín [junv], machupo [macv], and guanarito [gtov] viruses) can cause human disease ranging from mild febrile illness to a severe and often fatal hemorrhagic fever syndrome. these highly pathogenic viruses and the old world lassa fever virus pose a significant threat to public health and national security. the only licensed antiviral agent with activity against these viruses, ribavirin, has had mixed success in treating severe arenaviral disease and is associa ... | 2010 | 21115797 |
| development of peptide-conjugated morpholino oligomers as pan-arenavirus inhibitors. | members of the arenaviridae are a threat to public health and can cause meningitis and hemorrhagic fever, yet treatment options remain limited by a lack of effective antivirals. in this study, we found that peptide-conjugated phosphorodiamidate morpholino oligomers (ppmo) complementary to viral genomic rna were effective in reducing arenavirus replication in cell cultures and in vivo. ppmo complementary to the jun+¡n virus genome were designed to interfere with viral rna synthesis, translation, ... | 2011 | 21825302 |
| association of reduced interleukin-2 production with genetic susceptibility to pichinde virus in inbred strains of hamsters. | adult inbred mha hamsters are susceptible to lethal infections with pichinde virus while inbred lsh hamsters resist such infections. previous studies demonstrated higher levels of endogenous and induced natural killer (nk) activity in mha splenocytes than in lsh splenocytes. preferential replication of pichinde virus in cells with nk activity was suggested by showing that the greater numbers of infected spleen cells observed in mha hamsters could be accounted for by a cell population that cosedi ... | 1987 | 3028332 |
| ribonucleoprotein complexes associated with virions of pichinde virus and pichinde virus-infected cells. | | 1986 | 3724669 |
| regulation of pichinde virus replication in vero and bhk-21 cells. | | 1986 | 3724667 |
| studies concerning the relationship of pichinde virus-induced natural killer cells and cytotoxic t lymphocytes. | | 1986 | 3487704 |
| receptor tyrosine kinase inhibitors that block replication of influenza a and other viruses. | we have previously reported that two receptor tyrosine kinase inhibitors (rtkis), called ag879 and tyrphostin a9 (a9), can each block the replication of influenza a virus in cultured cells. in this study, we further characterized the in vitro antiviral efficacies and specificities of these agents. the 50% effective concentration (ec(50)) of each against influenza a was found to be in the high nanomolar range, and the selectivity index (si = 50% cytotoxic concentration [cc(50)]/ec(50)) was determ ... | 2011 | 21930873 |
| Effective oral favipiravir (T-705) therapy initiated after the onset of clinical disease in a model of arenavirus hemorrhagic Fever. | Lassa and Junín viruses are the most prominent members of the Arenaviridae family of viruses that cause viral hemorrhagic fever syndromes Lassa fever and Argentine hemorrhagic fever, respectively. At present, ribavirin is the only antiviral drug indicated for use in treatment of these diseases, but because of its limited efficacy in advanced cases of disease and its toxicity, safer and more effective antivirals are needed. | 2011 | 22022624 |
| polypeptide synthesis catalysed by components of pichinde virus disrupted by detergent. | pichinde virus preparations were investigated for ribosomal components and associated activities. after detergent treatment and fractionation, viral components were assayed for polypeptide synthesis, elongation of nascent polypeptide chains, and mrna activity. it was demonstrated that these subviral particles could synthesize polypeptides when exogenous mrna template, aminoacyl--trnas, translation factors, gtp and appropriate cations were added. undisrupted, whole virions could not synthesize po ... | 1981 | 7299369 |
| development of a new tacaribe arenavirus infection model and its use to explore antiviral activity of a novel aristeromycin analog. | a growing number of arenaviruses can cause a devastating viral hemorrhagic fever (vhf) syndrome. they pose a public health threat as emerging viruses and because of their potential use as bioterror agents. all of the highly pathogenic new world arenaviruses (nwa) phylogenetically segregate into clade b and require maximum biosafety containment facilities for their study. tacaribe virus (tcrv) is a nonpathogenic member of clade b that is closely related to the vhf arenaviruses at the amino acid l ... | 2010 | 20862280 |
| Use of recombinant adenovirus vectored consensus IFN-a to avert severe arenavirus infection. | Several arenaviruses can cause viral hemorrhagic fever, a severe disease with case-fatality rates in hospitalized individuals ranging from 15-30%. Because of limited prophylaxis and treatment options, new medical countermeasures are needed for these viruses classified by the National Institutes of Allergy and Infectious Diseases (NIAID) as top priority biodefense Category A pathogens. Recombinant consensus interferon alpha (cIFN-a) is a licensed protein with broad clinical appeal. However, while ... | 2011 | 22039436 |
| evaluation of plaque size reduction as a method for the detection of pichinde virus antibody. | the reaction between pichinde virus and homologous antisera has been studied using a plaque size reduction method. the incorporation of antiserum in the overlay of infected vero cell monolayers revealed a pattern of virus-cell interactions which were manifested by both a significant reduction in the diameter of virus plaques, and regeneration of cells in the centre of each. electron microscopy demonstrated that antibody molecules were bound to virus particles budding from the surface of infected ... | 1980 | 7425856 |
| size estimation of pichinde virus rna by gel electrophoresis under denaturing conditions. | rna extracted from purified pichinde virion preparations yields four major species, two of which appear to represent the viral genome while the other two appear to be cellular ribosomal 28s and 18s rna. the molecular weights of these rna species have been estimated by gel electrophoresis following denaturation by either methylmercury or glyoxal/dimethyl sulfoxide. the values determined by the two methods are in close agreement. the average molecular weights of l and s pichinde viral rna are 2.63 ... | 1980 | 7203968 |
| low-dose ribavirin potentiates the antiviral activity of favipiravir against hemorrhagic fever viruses. | favipiravir is approved in japan to treat novel or re-emerging influenza viruses, and is active against a broad spectrum of rna viruses, including ebola. ribavirin is the only other licensed drug with activity against multiple rna viruses. recent studies show that ribavirin and favipiravir act synergistically to inhibit bunyavirus infections in cultured cells and laboratory mice, likely due to their different mechanisms of action. convalescent immune globulin is the only approved treatment for a ... | 2016 | 26711718 |
| virion-associated ribosomes are not required for the replication of pichinde virus. | | 1977 | 196399 |
| strandedness of pichinde virus rna. | the pichinde virus rna did not possess the following characteristics of eucaryotic mrna: polyadenylic acid sequence, capped methylated structure, and ability to direct protein synthesis in vitro. polysomal rna extracted from cells infected with pichinde virus reannealed with 32p-labeled virus rna, protecting about 60% of the latter against rnase degestion. the polyadenylic acid-containing polysomal rna also reannealed to the 32p-labeled virus rna to approximately the same extent. these indicate ... | 1977 | 192915 |
| antigens of pichinde virus i. relationship of soluble antigens derived from infected bhk-21 cells to the structural components of the virion. | antigens detected by the complement-fixation (cf) test were prepared from bhk-21 cells infected with pichinde virus. the preparations contained two antigens demonstrable by immunodiffusion. the antigen present in abundance was heat stable, pronase resistant, and had a molecular weight of 20,000 to 30,000 as estimated by gel filtration. polyacrylamide gel electrophoresis of purified antigen demonstrated two low-molecular-weight polypeptides. an identical antigenic determinant was found by disrupt ... | 1977 | 67220 |
| identification of virulence determinants within the l genomic segment of the pichinde arenavirus. | several arenaviruses are responsible for causing viral hemorrhagic fevers (vhf) in humans. lassa virus (lasv), the causative agent of lassa fever, is a biosafety level 4 (bsl4) pathogen that requires handling in bsl4 facilities. in contrast, the pichinde arenavirus (picv) is a bsl2 pathogen that can cause hemorrhagic fever-like symptoms in guinea pigs that resemble those observed in human lassa fever. comparative sequence analysis of the avirulent p2 strain of picv and the virulent p18 strain sh ... | 2013 | 23552411 |
| differential inhibition of macrophage activation by lymphocytic choriomeningitis virus and pichinde virus is mediated by the z protein n-terminal domain. | several arenavirus pathogens, such as lassa and junin viruses, inhibit macrophage activation, the molecular mechanism of which is unclear. we show that lymphocytic choriomeningitis virus (lcmv) can also inhibit macrophage activation, in contrast to pichinde and tacaribe viruses, which are not known to naturally cause human diseases. using a recombinant pichinde virus system, we show that the lcmv z n-terminal domain (ntd) mediates the inhibition of macrophage activation and immune functions. | 2015 | 26423945 |
| serological evidence of infection by pichinde virus among laboratory workers. | a total of 44 laboratory workers were examined for serological evidence of infection by pichinde virus. complement-fixing antibodies were detected in the sera of 6 of 13 (46%) persons working with the virus but not among 31 persons not working with the virus. serological evidence of infection was greatest among those workers exposed to concentrated virus. no distinct illness could be associated with the infection. | 1974 | 4856825 |
| characterization of nucleic acid of pichinde virus. | the nucleic acid of pichinde virus was found to be single-stranded ribonucleic acid (rna) as determined by sensitivity to ribonuclease, by alkaline degradation, by buoyant density in cesium sulfate, and by analysis of the base composition. the rna of the virion could be separated into five components which had sedimentation coefficients corresponding to 31s, 28s, 22s, 18s and 4 to 6s. the 28s, 18s, and possibly the 4 to 6s rnas appear to be derived from host cell components incorporated into the ... | 1973 | 4734321 |
| the z proteins of pathogenic but not nonpathogenic arenaviruses inhibit rig-i-like receptor-dependent interferon production. | arenavirus pathogens cause a wide spectrum of diseases in humans ranging from central nervous system disease to lethal hemorrhagic fevers with few treatment options. the reason why some arenaviruses can cause severe human diseases while others cannot is unknown. we find that the z proteins of all known pathogenic arenaviruses, lymphocytic choriomeningitis virus (lcmv) and lassa, junin, machupo, sabia, guanarito, chapare, dandenong, and lujo viruses, can inhibit retinoic acid-inducible gene 1 (ri ... | 2015 | 25552708 |
| mhc basis of t cell-dependent heterologous immunity to arenaviruses. | having a history of infection with one pathogen may sometimes provide a level of t cell-dependent protective heterologous immunity to another pathogen. this immunity was initially thought due to cross-reactive t cell epitopes, but recent work has suggested that such protective immunity can be initiated nonspecifically by the action of cytokines on memory t cells. we retested this concept using two small and well-defined arenaviruses, lymphocytic choriomeningitis virus (lcmv) and pichinde virus ( ... | 2014 | 25094042 |
| loss of anti-viral immunity by infection with a virus encoding a cross-reactive pathogenic epitope. | t cell cross-reactivity between different strains of the same virus, between different members of the same virus group, and even between unrelated viruses is a common occurrence. we questioned here how an intervening infection with a virus containing a sub-dominant cross-reactive t cell epitope would affect protective immunity to a previously encountered virus. pichinde virus (pv) and lymphocytic choriomeningitis virus (lcmv) encode subdominant cross-reactive np₂₀₅₋₂₁₂ cd8 t cell epitopes sharin ... | 2012 | 22536152 |
| characterization of the glycoprotein stable signal peptide in mediating pichinde virus replication and virulence. | arenaviruses can cause lethal hemorrhagic fevers in humans with few preventative and therapeutic measures. the arenaviral glycoprotein stable signal peptide (ssp) is unique among signal peptides in that it is an integral component of the mature glycoprotein complex (gpc) and plays important roles not only in gpc expression and processing but also in the membrane fusion process during viral entry. using the pichinde virus (picv) reverse genetics system, we analyzed the effects of alanine substitu ... | 2016 | 27630230 |
| in vitro and in vivo characterizations of pichinde viral nucleoprotein exoribonuclease functions. | arenaviruses cause severe hemorrhagic fever diseases in humans, and there are limited preventative and therapeutic measures against these diseases. previous structural and functional analyses of arenavirus nucleoproteins (nps) revealed a conserved deddh exoribonuclease (rnase) domain that is important for type i interferon (ifn) suppression, but the biological roles of the np rnase in viral replication and host immune suppression have not been well characterized. infection of guinea pigs with pi ... | 2015 | 25878103 |
| [first evidence of lymphocytic choriomeningitis virus (arenavirus) infection in mus musculus rodents captured in the urban area of the municipality of sincelejo, sucre, colombia]. | the lymphocytic choriomeningitis virus is an old world arenavirus that infects mus musculus, and can cause congenital hydrocephalus, chorioretinitis and multisystemic failure in transplant human recipients. although the disease has not been clinically diagnosed in colombia yet, there have been reports of infection with the pichindé virus in rodents from cauca and valle del cauca departments, and with the guanarito virus in rodents from córdoba department. | 2017 | 28527269 |
| assays to assess arenaviral glycoprotein function. | arenaviruses, such as lassa virus (lasv) and pichindé virus (picv), are enveloped viruses with a bi-segmented ambisense rna genome. the large (l) genomic segment encodes the z matrix protein and the l rna-dependent rna polymerase, whereas the small (s) genomic segment encodes the nucleoprotein (np) and the glycoprotein precursor complex (gpc). gpc is processed by signal peptidase in the endoplasmic reticulum into the stable signal peptide (ssp) and gp1/gp2, which is further cleaved by the golgi- ... | 2018 | 28986832 |
| recombinant tri-segmented pichinde virus as a novel live viral vaccine platform. | pichinde virus (picv) is a nonpathogenic arenavirus with a bi-segmented rna genome (l and s segments) that encodes four viral genes. we have developed a reverse genetics system to generate recombinant tri-segmented picv (rp18tri) that packages three rna segments (l, s1, and s2) and can encode up to two foreign genes. using influenza virus ha and np as model antigens, we show that the rp18tri vector can induce strong humoral and cell-mediated immunity, which further increases upon a booster dose. ... | 2017 | 28374249 |
| characterization of the host response to pichinde virus infection in the syrian golden hamster by species-specific kinome analysis. | the syrian golden hamster has been increasingly used to study viral hemorrhagic fever (vhf) pathogenesis and countermeasure efficacy. as vhfs are a global health concern, well-characterized animal models are essential for both the development of therapeutics and vaccines as well as for increasing our understanding of the molecular events that underlie viral pathogenesis. however, the paucity of reagents or platforms that are available for studying hamsters at a molecular level limits the ability ... | 2015 | 25573744 |
| identification of critical amino acids within the nucleoprotein of tacaribe virus important for anti-interferon activity. | the arenavirus nucleoprotein (np) can suppress induction of type i interferon (ifn). this anti-ifn activity is thought to be shared by all arenaviruses with the exception of tacaribe virus (tcrv). to identify the tcrv np amino acid residues that prevent its ifn-countering ability, we created a series of np chimeras between residues of tcrv np and pichinde virus (picv) np, an arenavirus np with potent anti-ifn function. chimera np analysis revealed that a minimal four amino acid stretch derived f ... | 2013 | 23382389 |
| characterization of virulence-associated determinants in the envelope glycoprotein of pichinde virus. | we use a small animal model, based on guinea pigs infected with a non-pathogenic pichinde virus (picv), to understand the virulence mechanisms of arenavirus infections in the hosts. picv p2 strain causes a mild febrile reaction in guinea pigs, while p18 causes severe disease with clinical and pathological features reminiscent of lassa hemorrhagic fever in humans. the envelope glycoproteins (gpc) of p2 and p18 viruses differ at positions 119, 140, and 164, all localized to the receptor-binding g1 ... | 2012 | 22877842 |
| biological roles and functional mechanisms of arenavirus z protein in viral replication. | arenaviruses can cause severe hemorrhagic fever diseases in humans, with limited prophylactic or therapeutic measures. a small ring-domain viral protein z has been shown to mediate the formation of virus-like particles and to inhibit viral rna synthesis, although its biological roles in an infectious viral life cycle have not been directly addressed. by taking advantage of the available reverse genetics system for a model arenavirus, pichinde virus (picv), we provide the direct evidence for the ... | 2012 | 22761375 |
| generation of "natural killer cell-escape" variants of pichinde virus during acute and persistent infections. | pichinde virus (pv) strain an 3739 was determined to be sensitive to natural killer (nk) cells in vivo by enhanced replication in nk-cell-depleted mice. an nk-sensitive subclone (pv-nks1) was serially passed in mice whose nk cells had previously been activated by an interferon inducer, and two plaque isolates were shown to be resistant to nk cells but not to interferon. inoculation of severe-combined-immunodeficient mice with pv-nks1 led to a persistent infection resulting in an nk-resistant vir ... | 1992 | 1372371 |
| characterization of temperature-sensitive mutants of pichinde virus. | the synthesis of viral proteins and s rnas in cells infected with 12 temperature-sensitive (ts) mutants of pichinde virus was characterized. the mutants could be divided into five groups on the basis of the patterns of radiolabeled proteins immunoprecipitated from infected-cell lysates. markedly reduced nucleoprotein levels and undetectable amounts of glycoprotein precursor and l protein were synthesized at the nonpermissive temperature in cells infected with five of the mutants. reduced but det ... | 1988 | 3172336 |
| gene mapping in pichinde virus: assignment of viral polypeptides to genomic l and s rnas. | previous studies have demonstrated that pichinde virus encodes at least three primary translation products. using wild-type pichinde and munchique viruses and a reassortant between the two, designated re-2, we were able to assign polypeptides l, gpc, and np to viral l and s rnas. the re-2 virus contains the l rna of pichinde virus and the s rna of munchique virus. two-dimensional tryptic peptide mapping of l-[35s]methionine-containing peptides demonstrated that np and gpc were identical in munch ... | 1983 | 6302325 |
| synthesis of virus-specific polypeptides and genomic rna during the replicative cycle of pichinde virus. | a stock of plaque-purified pichinde virus, prepared under conditions designed to limit the amounts of defective interfering virus, was used to infect bhk cells. at daily intervals after infection, cells were examined for infectious and radiolabeled virus particle production and for the synthesis of virus-specific polypeptides. quantitative comparisons were also made of the concentrations of genomic pichinde virus l and s rnas in the cytoplasm of infected cells on different days after infection. ... | 1982 | 6287002 |
| characterization of polypeptides immunoprecipitable from pichinde virus-infected bhk-21 cells. | using hamster anti-pichinde virus serum, we immunoprecipitated polypeptides from bhk-21 cells infected with pichinde virus. seven immunoprecipitable polypeptides exhibited a time- and multiplicity of infection-dependent appearance when the cultures were pulse-labeled with l-[35s]methionine for 1 h. the predominant polypeptide was a nucleoprotein (np) of 64,000 daltons. components of 48,000, 38,000, and 28,000 daltons, when analyzed by two-dimensional tryptic peptide mapping, were found to be der ... | 1981 | 6264158 |
| pichinde virus l and s rnas contain unique sequences. | using oligodeoxyribonucleotides produced by limited dnase i digestion of calf thymus dna as a primer, we synthesized complementary dna (cdna) from the l and the s rnas of pichinde virus. the reaction conditions for in vitro cdna synthesis were optimized to allow transcription of about 90% of either l or s rna. no significant hybridization was observed when the l cdna was hybridized to the s rna, or when the s cdna was hybridized to the l rna. the results indicate that the l and s rnas of pichind ... | 1981 | 7218428 |
| treatment of late stage disease in a model of arenaviral hemorrhagic fever: t-705 efficacy and reduced toxicity suggests an alternative to ribavirin. | a growing number of arenaviruses are known to cause viral hemorrhagic fever (hf), a severe and life-threatening syndrome characterized by fever, malaise, and increased vascular permeability. ribavirin, the only licensed antiviral indicated for the treatment of certain arenaviral hfs, has had mixed success and significant toxicity. since severe arenaviral infections initially do not present with distinguishing symptoms and are difficult to clinically diagnose at early stages, it is of utmost impo ... | 2008 | 19008960 |
| development of real-time reverse transcriptase qpcr assays for the detection of punta toro virus and pichinde virus. | research with high biocontainment pathogens such as rift valley fever virus (rvfv) and lassa virus (lasv) is expensive, potentially hazardous, and limited to select institutions. surrogate pathogens such as punta toro virus (ptv) for rvfv infection and pichinde virus (picv) for lasv infection allow research to be performed under more permissive bsl-2 conditions. although used as infection models, ptv and picv have no standard real-time rt-qpcr assays to detect and quantify pathogenesis. ptv is a ... | 2016 | 27029488 |
| isolation of ribosome-like sturctures from pichinde virus. | three classes of mamalian ribosome-like structures were found to be associated with purified pichinde virus preparations. these structures, possessing sedimentation coefficients of 80s, 60s and 40s, were sensitive to edta dissociation and possessed a buoyant density in caesium chloride of 1-61 g/ml, a value analogous to that displayed by bhk21 cell ribosomes. analyses of rna components associated with ribosomal particles of pichinde virus established that 28s and 18s rnas could be extracted from ... | 1975 | 1168240 |
| arenaviruses: purification and physicochemical nature. | the arenaviruses are a group of enveloped viruses having as a unique morphological finding the presence in the virion of granules instead of a defined core. the viruses contain a single-stranded rna genome, but appreciable amounts of ribosomal-like rna and 4-6s rna of host cell origin have been detected. little information is available on the mode of replication of the viral nucleic acids. a virion-associated rna-dependent rna polymerase has been described and there is indirect evidence to sugge ... | 1975 | 1085204 |
| structural proteins of pichinde virus. | pichinde virus, a member of the arenovirus group, was found to have four polypeptides by polyacrylamide gel electrophoresis. two components, v(i) and v(ii), had molecular weights of about 72,000, whereas v(iii) had a molecular weight of 34,000. a minor component, v(iv), had a molecular weight of about 12,000. glucosamine was incorporated into v(ii) and v(iii), suggesting that these components were glycopeptides whereas v(i) and v(iv) were polypeptides. treatment of the virus with nonidet p-40 re ... | 1972 | 4673488 |
| pichindé virus, a new virus of the tacaribe group from colombia. | | 1971 | 4998616 |
| protective effect of anti-phosphatidylserine antibody in a guinea pig model of advanced hemorrhagic arenavirus infection. | host derived markers on virally infected cells or virions may provide targets for the generation of antiviral agents. recently, we identified phosphatidylserine (ps) as a host marker of virions and virally-infected cells. | 2017 | 29290843 |
| roles of arenavirus z protein in mediating virion budding, viral transcription-inhibition and interferon-beta suppression. | the smallest arenaviral protein is the zinc-finger protein (z) that belongs to the ring finger protein family. z serves as a main component required for virus budding from the membrane of the infected cells through self-oligomerization, a process that can be aided by the viral nucleoprotein (np) to form the viral matrix of progeny virus particles. z has also been shown to be essential for mediating viral transcriptional repression activity by locking the l polymerase onto the viral promoter in a ... | 2018 | 28986837 |
| assays to demonstrate the roles of arenaviral nucleoproteins (nps) in viral rna synthesis and in suppressing type i interferon. | arenaviruses, such as lassa virus (lasv) and pichindé virus (picv), are enveloped viruses with a bi-segmented ambisense rna genome. the large (l) genomic segment encodes the z matrix protein and the l rna-dependent rna polymerase, whereas the small (s) genomic segment encodes the nucleoprotein (np) and the glycoprotein (gpc). the np encapsidates viral genome, is required for viral transcription and replication, and acts as a type i interferon (ifn) antagonist. this article describes assays to de ... | 2018 | 28986834 |
| a novel live pichinde virus-based vaccine vector induces enhanced humoral and cellular immunity after a booster dose. | pichinde virus (picv) is a bisegmented enveloped rna virus that targets macrophages and dendritic cells (dcs) early in infection and induces strong innate and adaptive immunity in mice. we have developed a reverse genetics system to produce live recombinant picv (strain p18) with a trisegmented rna genome (rp18tri), which encodes all four picv gene products and as many as two foreign genes. we have engineered the vector to express the green fluorescent protein (gfp) reporter gene (abbreviated as ... | 2015 | 26676795 |
| distinctive rna transcriptase, polyadenylic acid polymerase, and polyuridylic acid polymerase activities associated with pichinde virus. | three rna polymerase activities were found and associated with purified pichinde virus, a member of the arenaviridae. a heat-labile polymerase activity which required all four ribonucleoside triphosphates for optimal activity co-sedimented on sucrose gradient centrifugation with the viral ribonucleoprotein complex from detergent-disrupted virus preparations. this enzyme synthesized heteropolymers which represented about 23% of the genome rna as determined by nucleic acid hybridization. two relat ... | 1979 | 225533 |
| [production of infectious virus and the accumulation in vero cells of pichinde virus antigens detectable by an indirect fluorescent antibody method]. | the dynamics of accumulation of infectious pichinde virus in the culture medium and virus-specific antigens in cells was studied in relation to multiplicity of infection in a multicycle experiment. differences in the fluorescence pattern of pichinde virus antigens in ifat were found to depend on the use of acetone or formaldehyde for fixation of the infected cells. | 2010 | 3020808 |
| establishment of bisegmented and trisegmented reverse genetics systems to generate recombinant pichindé viruses. | pichindé virus (picv), isolated from rice rats in colombia, south america, is an enveloped arenavirus with a bisegmented rna genome. the large (l) genomic segment encodes the z matrix protein and the l rna-dependent rna polymerase, whereas the small (s) genomic segment encodes the nucleoprotein (np) and the glycoprotein (gpc). this article describes the successful development of reverse genetics systems to generate recombinant picv with either a bisegmented or trisegmented genome. we have succes ... | 2018 | 28986840 |