Publications

changes in cell adhesion molecule expression on t cells associated with systemic virus infection.	virus-induced changes in adhesion molecule expression on t cells were investigated to understand how antiviral effector cells migrate into infectious foci. facs analysis revealed that after systemic infection with lymphocytic choriomeningitis virus a number of cell adhesion molecules, including vla-4, lfa-1, and icam-1, are up-regulated on cd8+ cells, whereas the lymph node homing receptor mel-14 is down-regulated during the infection; only marginal changes were observed for cd4+ cells. basicall ...	1994	7507962
analysis of pichinde arenavirus transcription and replication in human thp-1 monocytic cells.	human promonocytic thp-1 cells were previously shown to be nonpermissive for pichinde virus (pv) replication unless the cells were induced to differentiate to macrophages by stimulation with phorbol ester (pma) (j. virol. 65, 3575, 1991). the restriction did not involve receptor modulation, virus binding, nor internalization of virus but a requirement for a host cell function in pv replication was observed in that the phorbol ester effect required protein kinase c activation and was inhibited by ...	1995	7625125
tumor necrosis factor and the pathogenesis of pichinde virus infection in guinea pigs.	pichinde virus (pic) is a reticuloendothelial arenavirus of the new world tropics. a guinea pig passage-adapted strain of this virus (adpic) is uniformly lethal for inbred guinea pigs, while the related, prototype strain (pic3739) has attenuated virulence. the abilities of adpic and pic3739 to induce tumor necrosis factor (tnf) in vivo and in cultured macrophages were compared. infection with adpic, but not pic3739, was associated with detectable serum tnf that peaked in week 2 of infection. tum ...	1995	7694969
5' termini of pichinde arenavirus s rnas and mrnas contain nontemplated nucleotides.	primer extension of pichinde arenavirus purified virion rna suggests that genomes have at least a single nontemplated base at the 5' end which is a g in all cdna clones having one such single base. on the other hand, the predominant products of primer extension on total virus-infected-cell rna are at positions -1 and -2. the primer extension product at position -2 is not represented in virion rna, and neither of these products is proportionally represented in mrna. mrna is predominantly 3 or 4 b ...	1995	7707553
role of atrial natriuretic peptide in disturbed water and electrolyte metabolism of guinea pigs infected with pichinde virus.	daily intake and output of water and electrolytes (na+, k+, and cl-) were determined for 14 days in control and pichinde virus-infected strain-13 guinea pigs. although water intake began to decrease 7 days after virus inoculation, total daily water output (insensible water loss, urine excretion, plus fecal water loss) had little change. however, insensible water loss alone increased markedly in the virus-infected animals. both intake and excretions of urinary and fecal electrolytes decreased at ...	1995	8569144
persistent infection of mice with pichinde virus associated with failure to thrive.	intracranial inoculation of neonatal mice of certain inbred strains with pichinde virus has been found to be fatal, but balb/c neonates survive such infection. survival of balb/c mice after neonatal inoculation was not linked to the major histocompatability complex. virus was gradually cleared in surviving balb/c mice but could be detected in the brain and kidneys for up to 9 months after infection. these animals were not immunologically tolerant but exhibited high antibody titers to viral antig ...	1995	8577237
cd40l-deficient mice show deficits in antiviral immunity and have an impaired memory cd8+ ctl response.	the ligand for cd40 (cd40l) is expressed on the surface of activated cd4+ t cells and its role in t-b cell collaborations and thymus-dependent humoral immunity is well established. recently, by generating cd40l-knockout mice, we have confirmed its previously described role in humoral immunity and defined another important function of this molecule in the in vivo clonal expansion of antigen-specific cd4+ t cells. here, we investigated the potential in vivo role of cd40l in antiviral immunity by e ...	1996	8642323
reduction of otherwise remarkably stable virus-specific cytotoxic t lymphocyte memory by heterologous viral infections.	experimental analyses of the acute cytotoxic t lymphocyte (ctl) response to viruses have focused on studying these infections in immunologically naive hosts. in the natural environment, however, viral ctl responses occur in hosts that are already immune to other infectious agents. to address which factors contribute to the maintenance and waning of immunological memory, the following study examined the frequencies of virus-specific ctl precursor cells (pctl) not only using the usual experimental ...	1996	8676069
inhibition of arenavirus multiplication in vitro by phenotiazines.	trifluoperazine (tfp) and chlorpromazine (cpz), two pharmacologically active phenotiazine derivatives, were evaluated for their inhibitory activity on the replication of the arenaviruses junin (jv), the etiological agent of argentine hemorrhagic fever, tacaribe virus and pichinde virus. both compounds achieved a concentration-dependent inhibition of viral multiplication at concentrations not affecting cell viability. the 50% inhibitory concentration (ic50) values determined by a virus yield inhi ...	1996	8811199
the lassa fever virus l gene: nucleotide sequence, comparison, and precipitation of a predicted 250 kda protein with monospecific antiserum.	the large (l) rna segment of lassa fever virus (las) encodes a putative rna-dependent rna polymerase (rdrp or l protein). similar to other arenaviruses, the las l protein is encoded on the genome-complementary strand and is predicted to be 2218 amino acids in length (253 kda). it has an unusually large non-coding region adjacent to its translation start site. the las l protein contains six motifs of conserved amino acids that have been found among arenavirus l proteins and core rdrp of other seg ...	1997	9049403
sequence analysis of the small rna segment of guinea pig-passaged pichinde virus variants.	the established animal model for lassa fever is based on the new world arenavirus pichinde (pic). natural isolates of pic virus are attenuated in guinea pigs, but serial guinea pig passage renders them extremely virulent in that host. we have compared the nucleotide sequences of the small rna segments of two attenuated, low-passage variants of the pic virus munchique strain (coan 4763) and two virulent, high-passage derivatives. missense mutations in the glycoprotein precursor (gpc) gene at codo ...	1999	10463670
virus-induced abrogation of transplantation tolerance induced by donor-specific transfusion and anti-cd154 antibody.	treatment with a 2-week course of anti-cd154 antibody and a single transfusion of donor leukocytes (a donor-specific transfusion or dst) permits skin allografts to survive for >100 days in thymectomized mice. as clinical trials of this methodology in humans are contemplated, concern has been expressed that viral infection of graft recipients may disrupt tolerance to the allograft. we report that acute infection with lymphocytic choriomeningitis virus (lcmv) induced allograft rejection in mice tr ...	2000	10666251
antiviral and virucidal activities against arenaviruses of zinc-finger active compounds.	fifteen antiretroviral zn-finger active compounds with diverse chemical structures, including azoic compounds, hydrazide derivatives, disulphide-based reagents and others were screened in vitro against junin virus (junv), the aetiological agent of argentine haemorrhagic fever, by a virus yield inhibition assay in vero cells. cytotoxicity was evaluated simultaneously by the mtt method. of the compounds, three were totally inactive as antivirals, nine presented moderate anti junv-activity and thre ...	2000	10901294
nucleotide sequence of the pirital virus (family arenaviridae) small genomic segment.	pirital virus is a newly discovered south american member of the family arenaviridae. we determined that the complete nucleotide sequence of the small genomic segment of pirital virus is 3393 nt long, and encodes the viral nucleoprotein (n) and glycoprotein precursor (gpc) (561 aa and 509 aa, respectively) in nonoverlapping open reading frames of opposite polarities. the n and gpc genes are separated by an intergenic region that is 80 nt long; the predicted secondary structure of this region inc ...	2001	11162687
reassortant analysis of guinea pig virulence of pichinde virus variants.	the new world arenavirus pichinde (pic) is the basis of an accepted small animal model for human lassa fever. pic (munchique strain) variant p2 is attenuated in guinea pigs, whereas variant p18 is extremely virulent. previous sequence analysis of the s segments of these two viruses indicated a small number of possible virulence markers in the glycoprotein precursor (gpc) and nucleoprotein (np) genes. in order to determine the role of these s segment genes in guinea pig virulence in this system, ...	2001	11883003
characterization of the glycoproteins of crimean-congo hemorrhagic fever virus.	crimean-congo hemorrhagic fever (cchf) virus is the cause of an important tick-borne disease of humans throughout regions of africa, europe, and asia. like other members of the genus nairovirus, family bunyaviridae, the cchf virus m genome rna segment encodes the virus glycoproteins. sequence analysis of the cchf virus (matin strain) m rna segment revealed one major open reading frame that potentially encodes a precursor polyprotein 1,689 amino acids (aa) in length. comparison of the deduced ami ...	2002	12072526
alterations in nf-kappab and rbp-jkappa by arenavirus infection of macrophages in vitro and in vivo.	pichinde virus is an arenavirus that infects guinea pigs and serves as an animal model for human lassa fever. an attenuated pichinde virus variant (p2) and a virulent variant (p18) are being used to delineate pathogenic mechanisms that culminate in shock. in guinea pigs, the infection has been shown to begin in peritoneal macrophages following intraperitoneal inoculation and then spreads to the spleen and other reticuloendothelial organs. we show here that infection of the murine monocytic cell ...	2002	11773391
phylogeny of the venezuelan arenaviruses.	guanarito virus (the etiologic agent of venezuelan hemorrhagic fever, vhf) and pirital virus coexist in the region of venezuela in which venezuelan hemorrhagic fever is endemic. the purpose of this study was to extend our knowledge of the evolutionary relationship between these two arenaviruses. we determined that the large genomic segments of guanarito virus and pirital virus are similar in size and identical in structural organization to the large genomic segments of other south american arena ...	2004	15084402
private specificities of cd8 t cell responses control patterns of heterologous immunity.	cd8 t cell cross-reactivity between viruses can play roles in protective heterologous immunity and damaging immunopathology. this cross-reactivity is sometimes predictable, such as between lymphocytic choriomeningitis virus (lcmv) and pichinde virus, where cross-reactive epitopes share six out of eight amino acids. here, however, we demonstrate more subtle and less predictable cross-reactivity between lcmv and the unrelated vaccinia virus (vv). epitope-specific t cell receptor usage differed bet ...	2005	15710651
evaluating the immunogenicity and protective efficacy of a dna vaccine encoding lassa virus nucleoprotein.	several viruses in the arenavirus genus of the family arenaviridae cause severe, often fatal, hemorrhagic fever. one such virus, lassa virus (lv), is a frequent cause of disease in africa, and survivors often are left with substantial neurological impairment. the feasibility of protective immunization against lv infection, and the associated disease, has been demonstrated in animal models, using recombinant vaccinia viruses to deliver lassa proteins. circumstantial evidence implicates cellular i ...	2005	15823608
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
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
superinfection exclusion in bhk-21 cells persistently infected with junín virus.	we characterized a persistently junín virus (junv)-infected bhk-21 cell line obtained by experimental infection with the xjcl3 strain. this cell line, named k3, produced low levels of virus in supernatants which were not influenced by the presence of defective interfering (di) particles after the first year of infection. k3 cells were able to exclude superinfection of the homologous junv and the antigenically related tacaribe virus (tcrv), whereas the non-related arenaviruses lymphocytic choriom ...	2007	17872526
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
pichindé virus is trafficked through a dynamin 2 endocytic pathway that is dependent on cellular rab5- and rab7-mediated endosomes.	pichindé virus (picv) is a new world arenavirus that has been shown to enter cells through a clathrin-dependent endocytic pathway. in this study, we determined that picv is trafficked through the cellular dynamin 2 (dyn2) endocytic pathway. additionally, the data suggest that picv entry is ph-dependent and that the virus travels through rab5-mediated early and rab7-mediated late endosomes. in all, this study characterizes the endocytic pathway utilized by the arenavirus picv.	2008	18543061
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
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
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
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
analysis of the differential host cell nuclear proteome induced by attenuated and virulent hemorrhagic arenavirus infection.	arenaviruses are important emerging pathogens and include a number of hemorrhagic fever viruses classified as niaid category a priority pathogens and cdc potential biothreat agents. infection of guinea pigs with the new world arenavirus pichindé virus (picv) has been used as a biosafety level 2 model for the lassa virus. despite continuing research, little is known about the molecular basis of pathogenesis, and this has hindered the design of novel antiviral therapeutics. modulation of the host ...	2009	19004951
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
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
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
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
[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
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
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
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
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 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
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
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
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
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
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
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
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
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
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
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
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
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
[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
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
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
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
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
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