Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “VIRUSES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 91 records · Page 5Linked to original sources
PubMed2000

Human parainfluenza virus type 3 (PIV3) expressing the hemagglutinin protein of measles virus provides a potential method for immunization against measles virus and PIV3 in early infancy.

Recombinant human parainfluenza virus type 3 (PIV3) was used as a vector to express the major protective antigen of measles virus, the hemagglutinin (HA) glycoprotein, in order to create a bivalent PIV3-measles virus that can be administered intranasally. The measles virus HA open reading frame (ORF) was inserted as an additional transcriptional unit into the N-P, P-M, or HA-neuraminidase (HN)-L gene junction of wild-type PIV3 or into the N-P or P-M gene junction of an attenuated derivative of PIV3, termed rcp45L. The recombinant PIV3 (rPIV3) viruses bearing the HA inserts replicated more slowly in vitro than their parental viruses but reached comparable peak titers of >/=10(7.5) 50% tissue culture infective doses per ml. Each of the wild-type or cold-passaged 45L (cp45L) PIV3(HA) chimeric viruses replicated 5- to 10-fold less well than its respective parent virus in the upper respiratory tract of hamsters. Thus, insertion of the approximately 2-kb ORF itself conferred attenuation, and this attenuation was additive to that conferred by the cp45L mutations. The attenuated cp45L PIV3(HA) recombinants induced a high level of resistance to replication of PIV3 challenge virus in hamsters and induced very high levels of measles virus neutralizing antibodies (>1:8,000) that are well in excess of those known to be protective in humans. rPIV3s expressing the HA gene in the N-P or P-M junction induced about 400-fold more measles virus-neutralizing antibody than did the rPIV3 with the HA gene in the HN-L junction, indicating that the N-P or P-M junction appears to be the preferred insertion site. Previous studies indicated that the PIV3 cp45 virus, a more attenuated version of rcp45L, replicates efficiently in the respiratory tract of monkeys and is immunogenic and protective even when administered in the presence of very high titers of passively transferred PIV3 antibodies (A. P. Durbin, C. J. Cho, W. R. Elkins, L. S. Wyatt, B. Moss, and B. R. Murphy, J. Infect. Dis. 179:1345-1351, 1999). This suggests that this intranasally administered PIV3(HA) chimeric virus can be used to immunize infants with maternally acquired measles virus antibodies in whom the current parenterally administered live measles virus vaccine is ineffective.

Animals↗
PubMed1994

Temporal profile of hepatitis C virus antibody and genome in infants born to mothers infected with hepatitis C virus but without human immunodeficiency virus coinfection.

To investigate mother-to-infant transmission of hepatitis C virus, serial follow-up of anti-HCV and hepatitis C virus RNA was undertaken in 11 infants born to hepatitis C virus-infected mothers who had been screened from 11,688 pregnant women. None of the hepatitis C virus-infected mothers was infected by human immunodeficiency virus. Anti-HCV was checked by the second-generation enzyme immunoassay kit, and hepatitis C virus RNA was examined by reverse transcriptase-nested polymerase chain reaction. Hepatitis C virus RNA was found in more than two serum samples in two of these 11 infants; those two infants were regarded as hepatitis C virus-infected. One of the two had hepatitis C virus RNA at the age of 1, 3, and 6 months, but not later. The course of hepatitis C virus RNA and anti-HCV in this baby may reflect fluctuating viral replication in chronic infectious disease or viral clearance in acute infection. The other infant had hepatitis C virus RNA detectable at the age of 3 months and at 15, 18 and 24 months. In the other nine non-hepatitis C virus-infected infants, maternally acquired anti-HCV gradually disappeared by the age of 6 months. The liver function profile fell to the normal range in all the infants, including the two hepatitis C virus-infected infants. This may indicate the subclinical nature of hepatitis C virus infection in infancy. Seven fathers and four siblings of these 11 infants were checked for anti-HCV and liver function tests; none had evidence of hepatitis C virus infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1991

Homotypic and heterotypic protection against influenza virus infection in mice by recombinant vaccinia virus expressing the haemagglutinin or nucleoprotein of influenza virus.

Recombinant vaccinia virus expressing the influenza virus haemagglutinin (HA) or nucleoprotein (NP) genes from A/SW/Hong Kong/1/74 (H1N1) under the control of a hybrid promoter containing the P7.5 early promoter element and promoter of the gene encoding the major protein of cowpox virus A type inclusion body was constructed to investigate protective immunity against homologous and heterologous viruses in mice. These recombinant vaccinia viruses produced authentic influenza virus HA and NP in infected cells. The recombinant vaccinia virus-influenza virus HA conferred efficient subtype-specific protection although mice challenged with heterologous influenza viruses underwent initial infection. By contrast, immunization with the recombinant vaccinia-influenza virus NP limited virus multiplication in the lungs against challenge infection with all H1N1 and H3N2 influenza viruses examined, although less efficiently. These results will prompt the re-examination of the possibility of using the recombinant vaccinia virus-influenza virus NP as a cross-protective vaccine.

Animals↗
PubMed1980

Mode of subacute sclerosing panencephalitis (SSPE) virus infection in tissue culture cells. II. Cell-free viruses in cell cultures infected with Kitaken-1 and Biken strains of SSPE virus.

Cell-free infectious viruses were successfully recovered by the aid of freezing and thawing from cultures infected with the Kitaken-1 and Biken strains of subacute sclerosing panencephalitis (SSPE) virus. Our results including those in a previous report which dealt with the Niigata-1 strain of SSPE virus show that cell-free viruses can be detected from all of the SSPE virus-carrying cultures established in Japan. It was also found that cell-free infectious viruses can be recovered efficiently by dispersing the virus-carrying cultures with EDTA. The inclusion of trypsin in the EDTA solution, however, caused a poor recovery of the infectious viruses. Infection of cells with the cell-free viruses readily established the virus-carrying cultures that have characteristics comparable to those of their original cultures. The culture infected with the Kitaken-1 strain produced infectious viruses in about ten times the amount of the other two infected cultures. The buoyant densities of the cell-free infectious viruses were almost the same among the three strains, the values being 1.120 to 1.132, but significantly less than that of 1.164 of measles virus. The low density can be ascribed to one of the characteristics of these SSPE viruses.

Cell Line↗
PubMed1988

Transforming viruses spontaneously arise from nontransforming reticuloendotheliosis virus strain T-derived viruses as a result of increased accumulation of spliced viral RNA.

The highly oncogenic avian retrovirus reticuloendotheliosis virus strain T (Rev-T) contains a substitution of the oncogene v-rel for much of env and a deletion of gag and pol relative to the helper virus Rev-A. Replacement of gag and pol sequences in Rev-T suppresses transformation by reducing the accumulation of spliced viral mRNA and v-rel protein in infected cells (C. K. Miller and H. M. Temin, J. Virol 58:75-80, 1986). After infection of spleen cells with viruses containing gag and pol sequences, revertant viruses that are strongly transforming were found. Approximately three-fourths of the revertant viruses appeared structurally the same as the parental virus, and approximately one-fourth of the revertant viruses had large deletions (similar in size and location to the deletion in Rev-T). Two revertant viruses that appeared structurally the same as the parental virus were molecularly cloned. The regions sufficient to change the parental virus to a strongly transforming virus were determined by construction of recombinant viruses. In one revertant virus, the region sufficient for transformation contained a 327-base-pair insertion 5' of the 3' splice site used by Rev-T. In the other revertant virus, the region sufficient for transformation contained a 1-base-pair transition and a deletion of one copy of a 9-base-pair direct repeat, both 3' of the 3' splice site used by Rev-T. These differences resulted in the accumulation of increased levels of subgenomic v-rel mRNA and protein, ultimately leading to transformation.

Animals↗
PubMed1983

Abelson murine leukemia virus: effect of helper virus from regressing Friend virus on leukemia development.

Replication defective Abelson murine leukemia virus (A-MuLV) induces a non-thymic lymphoma in vivo and transforms both hematopoietic and fibroblastic cells in vitro. In vivo leukemogenicity and the efficiency of in vitro transformation of hematopoietic cells by A-MuLV are known to be affected by the replication competent helper virus present in A-MuLV stocks. The helper virus isolated from the regressing strain of Friend virus (RF-MuLV) is responsible for the spontaneous regression of erythroleukemia induced by replication defective spleen-focus forming virus and itself induces a lymphocytic leukemia which spontaneously regresses. The diseases produced by A-MuLV stocks containing either RF-MuLV or Moloney leukemia virus, the helper virus associated with the original isolate of A-MuLV, were compared to determine if RF-MuLV can influence the disease produced by a replication defective virus with a discrete transforming gene. Both virus stocks induced leukemias with similar efficiency and gross pathology. Spontaneous regression was not observed when RF-MuLV was used as the helper virus. Examination of the leukemic cells and cell lines derived from leukemic tissues indicated that the target cell for A-MuLV transformation was not affected by the helper virus. Both transformed lymphoid and monocytic cells were cultured from leukemic tissues and established as cell lines. The lymphoid cells were phenotypically similar to pre-B cells or null cells, while the monocytic cell lines resemble promonocytes. The frequency with which promonocytic cell lines were isolated from leukemic mice suggests that A-MuLV leukemogenesis may often involve transformation of monocytic series cells as well as lymphoid cells. Thus, RF-MuLV can serve as an efficient helper virus for A-MuLV and does not appear to alter the in vivo target cell for transformation. It is unable, however, to alter the progressive course of Abelson virus induced disease.

Abelson murine leukemia virus↗
PubMed1952

Effect of sodium monofluoroacetate on the multiplication of influenza viruses, mumps virus and pneumonia virus of mice (PVM).

Sodium fluoroacetate, given after virus inoculation in doses of 3 to 4 mg. per kg. in mice or 2 mg. in chick embryos, caused only a slight delay in the multiplication of the PR8 strain of influenza A virus in the mouse lung and of PR8 or the Lee strain of influenza B virus in the allantoic sac. The quantities of the compound used were sufficient to cause approximately 10 to 20 per cent mortality in mice and 100 per cent in chick embryos. The use of small virus inocula did not markedly increase the effect of sodium fluoroacetate on the multiplication of PR8 or Lee in the chick embryo and maximal titers were obtained in all cases. In contrast to the findings in the chick embryo, sodium fluoroacetate caused a definite delay in the multiplication of Lee virus in the mouse lung but did not affect the final virus titer. Sodium fluoroacetate in like amounts caused only a minimal delay in the multiplication of pneumonia virus of mice (PVM) in the mouse lung or of mumps virus in the chick embryo. With both PVM and mumps virus, maximal titers were obtained almost simultaneously in fluoroacetate and control animals. When three daily injections of the compound were given to mice infected previously with PVM, a definite diminution in the virus titer was demonstrable. However, pretreatment with three daily injections of the compound caused no alteration in the capacity of mice to support the multiplication of PVM. From the results of these experiments, it appears that the cellular metabolic processes blocked by sodium fluoroacetate are not essential for the multiplication of influenza viruses, mumps virus, or pneumonia virus of mice (PVM).

Animals↗
PubMed1988

Physicochemical properties of Marburg virus: evidence for three distinct virus strains and their relationship to Ebola virus.

The physicochemical and antigenic properties of three groups of Marburg (MBG) virus isolates, separated temporally and geographically, were compared to each other and to another member of the same family, Ebola (EBO) virus. Each MBG isolate contained seven virion proteins, one of which was a glycosylated surface protein. Peptide mapping of glycoproteins, nucleoproteins (NP) and viral structural protein (VP40) demonstrated extensive sequence conservation in the proteins of viruses isolated over a 13-year period, but homology was not evident in VP24. Some homology between the NPs of MBG and EBO was observed. A close antigenic relationship between MBG strains was found by radioimmunoassay but no evidence was found of antigenic cross-reactivity with EBO viruses. MBG virion proteins are produced from virus-specific monocistronic mRNA species. Five of the seven viral proteins were produced by in vitro translation of these RNAs. MBG virions contained one RNA species with an Mr of 4.2 x 10(6) and virions had a density of 1.14 g/ml in potassium tartrate. Virus isolates from different outbreaks had distinct T1 oligonucleotide maps, but had approximately 95% homology in base sequence. No two geographically distinct virus pairs were more closely related to each other than to a third virus isolate. MBG viruses are thus similar to EBO viruses in morphology and other physicochemical properties and are very similar to each other in RNA and protein composition. Each of the three geographically and temporally distinct MBG virus outbreaks appears to have been due to a genetically distinguishable, but antigenically closely related virus strain. In addition, these studies confirm the belief that MBG and EBO viruses are members of the new virus family, the Filoviridae.

Animals↗
PubMed2005

Prevalence of human polyoma virus (BK virus and JC virus) infection in patients with chronic renal disease.

BACKGROUND: Polyoma virus infection in renal transplant patients is sometimes critical in graft survival. But, to date, polyoma virus infection or reactivation has not been checked before renal transplantation. The prevalence of polyoma viruses (BK virus and JC virus) was investigated in 45 patients with renal disease who were future candidates as renal graft recipients. METHODS: Because these viruses are excreted in urine, the urine of these 45 patients was analyzed by polymerase chain reaction (PCR). The urine of 37 age-matched normal subjects (control group) was also investigated. RESULTS: In the control group, 13.5% of the normal subjects were positive for BK virus and 24.3% were positive for JC virus. In the patients with renal disease, 33.3% were positive for BK virus and 33.3% were positive for JC virus; the prevalence of BK virus infection was significantly higher than that in the normal subjects. Patients with renal disease with corticosteroid therapy revealed an especially high prevalence of BK virus infection (55.6%), indicating the possibility of viral reactivation by corticosteroid therapy. CONCLUSIONS: More attention should be paid to polyoma virus infection in candidates for renal transplantation with a previous therapeutic history of corticosteroid administration.

Adrenal Cortex Hormones↗
PubMed2005

Pathogenicity of influenza viruses with genes from the 1918 pandemic virus: functional roles of alveolar macrophages and neutrophils in limiting virus replication and mortality in mice.

The Spanish influenza pandemic of 1918 to 1919 swept the globe and resulted in the deaths of at least 20 million people. The basis of the pulmonary damage and high lethality caused by the 1918 H1N1 influenza virus remains largely unknown. Recombinant influenza viruses bearing the 1918 influenza virus hemagglutinin (HA) and neuraminidase (NA) glycoproteins were rescued in the genetic background of the human A/Texas/36/91 (H1N1) (1918 HA/NA:Tx/91) virus. Pathogenesis experiments revealed that the 1918 HA/NA:Tx/91 virus was lethal for BALB/c mice without the prior adaptation that is usually required for human influenza A H1N1 viruses. The increased mortality of 1918 HA/NA:Tx/91-infected mice was accompanied by (i) increased (>200-fold) viral replication, (ii) greater influx of neutrophils into the lung, (iii) increased numbers of alveolar macrophages (AMs), and (iv) increased protein expression of cytokines and chemokines in lung tissues compared with the levels seen for control Tx/91 virus-infected mice. Because pathological changes in AMs and neutrophil migration correlated with lung inflammation, we assessed the role of these cells in the pathogenesis associated with 1918 HA/NA:Tx/91 virus infection. Neutrophil and/or AM depletion initiated 3 or 5 days after infection did not have a significant effect on the disease outcome following a lethal 1918 HA/NA:Tx/91 virus infection. By contrast, depletion of these cells before a sublethal infection with 1918 HA/NA:Tx/91 virus resulted in uncontrolled virus growth and mortality in mice. In addition, neutrophil and/or AM depletion was associated with decreased expression of cytokines and chemokines. These results indicate that a human influenza H1N1 virus possessing the 1918 HA and NA glycoproteins can induce severe lung inflammation consisting of AMs and neutrophils, which play a role in controlling the replication and spread of 1918 HA/NA:Tx/91 virus after intranasal infection of mice.

Animals↗
PubMed1998

A virus with a mutation in the ICP4-binding site in the L/ST promoter of herpes simplex virus type 1, but not a virus with a mutation in open reading frame P, exhibits cell-type-specific expression of gamma(1)34.5 transcripts and latency-associated transcripts.

The herpes simplex virus type 1 L/S junction-spanning transcripts (L/STs) are a family of multisized transcripts expressed at high levels in cells infected with mutant viruses that (i) do not express ICP4, (ii) specify forms of ICP4 unable to bind to the consensus ICP4 binding site, or (iii) contain mutations in the ICP4 binding site located at the transcriptional start site of the L/STs. By extension, the failure to detect the L/STs in wild-type virus-infected cells is due to the repressive effect of ICP4 bound to its cognate binding site upstream of the L/ST transcription initiation site. ORF-P, the first and largest open reading frame (ORF) encoded by the L/STs, overlaps >90% of the ORF encoding ORF-34.5, a putative neurovirulence factor, which is transcribed from the opposite DNA strand. Viruses with mutations in the overlapping region of ORF-P and ICP34.5 exhibit premature shutoff of infected-cell protein synthesis and are highly attenuated following intracranial inoculation of juvenile mice. To determine whether the premature protein shutoff and neuroattenuated phenotypes of ORF-P ORF-34.5 double mutants are a consequence of alterations in ORF-P, ORF-34.5, or both, viruses containing mutations only in ORF-P or only in the ICP4 binding site in the L/ST promoter were isolated and characterized. Mutant virus L/ST-n38 contains a single-base-pair transition mutation in ORF-P codon 38, resulting in translational termination of the ORF-P protein (OPP). This mutation does not alter the amino acid sequence of ICP34.5. Expression of a truncated form of OPP by mutant virus L/ST-n38 did not result in premature shutoff of infected-cell protein synthesis and produced no other observable phenotype relative to wild-type virus in in vitro tests. Moreover, the 50% lethal dose (LD50) of L/ST-n38 was comparable to that of wild-type virus following intracranial inoculation of 3-week-old mice, as were the latency and reactivation phenotypes of the virus. These properties of L/ST-n38 indicate that the attenuated phenotype of ORF-P ORF-34.5 double mutants is a consequence of mutations that affect the function of ICP34.5 and not the function of OPP. Mutant virus LST-4BS contains four single-base-pair substitutions in the ICP4 binding site in the L/ST promoter that abrogate the binding of ICP4 to this site, leading to high-level expression of the L/STs and OPP. LST-4BS induced premature shutoff of viral and cellular protein synthesis and was slightly growth restricted in cells of neural lineage (SK-N-SH human neuroblastoma cells) but was wild type for these two parameters in cells of nonneural lineage (immortalized primate Vero cells). Of particular interest was the observation that L/ST-4BS exhibited cell-type-specific expression of both the gamma(1)34.5 transcripts and the latency-associated transcripts (LATs). Thus, expression of these transcripts was barely detectable in cells of neural lineage (NB41A3 mouse neuroblastoma cells) but was wild type in Vero cells. In vivo, L/ST-4BS was reactivated from mouse trigeminal ganglia with reduced efficiency and delayed kinetics relative to wild-type virus. L/ST-4BS was completely attenuated for neurovirulence (LD50 > 10(6) PFU) relative to wild-type virus (LD50 < 900 PFU), although the four single-base-pair substitutions lie outside the coding region for the neurovirulence factor, ICP34.5. Collectively, the complex in vitro and in vivo phenotypes of L/ST-4BS can be attributed to (i) disruptions of the ICP4 binding site in the L/ST promoter and subsequent overexpression of the L/STs and OPP; (ii) alterations in ORF-O, which is also mutated in L/ST-4BS; or (iii) alterations in other cryptic genes or cis-acting elements.

Amino Acid Sequence↗
PubMed2001

Functional murine leukemia virus vectors pseudotyped with the visna virus envelope show expanded visna virus cell tropism.

Pseudotype virus vectors serve as a powerful tool for the study of virus receptor usage and entry. We describe the development of murine leukemia virus (MuLV) particles pseudotyped with the visna virus envelope glycoprotein and encoding a green fluorescent protein reporter as a tool to study the expression of the visna virus receptor. Functional MuLV/visna virus pseudotypes were obtained when the cytoplasmic tail of the visna virus envelope TM protein was truncated to 3, 7, or 11 amino acids in length. MuLV/visna virus particles were used to transduce a panel of cell types from various organisms, including sheep, goat, human, hamster, mouse, monkey, and quail. The majority of the cells examined were susceptible to MuLV/visna pseudotype viruses, supporting the notion that the visna virus cellular receptor is a widely expressed protein found in many species. Of 16 different cell types tested, only mouse embryo fibroblast NIH 3T3 cells, hamster ovary CHO cells, and the human promonocyte cell line U937 cells were not susceptible to transduction by the pseudotyped virus. The production of functional MuLV/visna virus pseudotypes has provided a sensitive, biologically relevant system to study visna virus cell entry and envelope-receptor interactions.

Amino Acid Sequence↗
PubMed1992

Intrahepatic expression of pre-S1 and pre-S2 antigens in chronic hepatitis B virus infection in relation to hepatitis B virus replication and hepatitis delta virus superinfection.

Hepatocyte expression of pre-S1 and pre-S2 in relation to hepatitis B virus replication (hepatitis B virus-DNA in serum and HBcAg in the liver), histological activity and hepatitis delta virus superinfection was studied by indirect immunofluorescence on frozen sections of liver specimens from 68 patients with chronic hepatitis B virus infection. All 44 patients with chronic type B hepatitis had pre-S1 and pre-S2 display in the liver. The distribution of pre-S1 in the liver was membranous in one, mixed membranous and cytoplasmic in 12, and cytoplasmic in 31. The distribution of pre-S2 was membranous in one, mixed membranous and cytoplasmic in 26, and cytoplasmic in 17. Membranous expression of pre-S1 was significantly more prevalent in patients with active hepatitis B virus replication than in those without (13/28 v 0/16, p < 0.001), regardless of the histological activity, as was membranous expression of pre-S2 (27/28 v 0/16, p < 0.001). In contrast, a significantly higher extent of cytoplasmic expression of pre-S1 and pre-S2 was noted in patients without active hepatitis B virus replication than in those with. Of 24 patients with chronic type D hepatitis virus, eight had active hepatitis B virus replication, and the other 16 did not. The distribution and quantitative expression of pre-S1 and pre-S2 in the liver in these patients also correlated significantly with the status of hepatitis B virus replication and, moreover, showed little or no difference from those without hepatitis delta virus infection. In conclusion, all patients with chronic type B hepatitis had synthesis and display of pre-S1 and pre-S2 in the liver. The distribution and quantitative expression of pre-S1 and pre-S2, however, were closely related to the status of hepatitis B virus replication, but not to the histological activity. Hepatocyte expression of pre-S1 and pre-S2 in chronic type D hepatitis also correlated significantly with status of hepatitis B virus replication, and was not modulated by concurrent hepatitis delta virus infection.

Fluorescent Antibody Technique↗
PubMed1998

Rapid simultaneous diagnosis of infections with respiratory syncytial viruses A and B, influenza viruses A and B, and human parainfluenza virus types 1, 2, and 3 by multiplex quantitative reverse transcription-polymerase chain reaction-enzyme hybridization assay (Hexaplex).

A multiplex quantitative reverse transcription-polymerase chain reaction-enzyme hybridization assay (Hexaplex; Prodesse, Milwaukee) was developed and used to rapidly detect and quantitate RNA of respiratory syncytial viruses A and B, influenza viruses A and B, and human parainfluenza virus types 1, 2, and 3 in nasal wash specimens in a single test. Primers and probes originated from highly conserved regions of each viral genome. Six and a half primer pairs were mixed for the simultaneous detection and quantitation of RNA from seven different respiratory viruses. We tested 109 clinical samples with this assay. Twenty-nine virus culture-positive samples were all positive by Hexaplex. Samples from 40 symptomatic patients were negative by virus culture, but eight of these were positive by Hexaplex. Forty samples from asymptomatic children were negative by both virus culture and Hexaplex. No cross-reactions were noted among 17 different respiratory viruses with use of this assay. Hexaplex was 100% sensitive (95% confidence interval [CI], 0.88-1.0) and 98% specific (95% CI, 0.97-0.99). All eight "false-positive" Hexaplex results (in comparison with negative viral culture results) were for symptomatic patients with low numbers of virus RNA copies. This finding suggests that Hexaplex may be more sensitive than virus culture. Our data demonstrate that Hexaplex is a rapid, sensitive, and specific quantitative test for the diagnosis of infections with these seven common respiratory viruses.

Humans↗
PubMed1996

Avian reovirus-induced syncytium formation is independent of infectious progeny virus production and enhances the rate, but is not essential, for virus-induced cytopathology and virus egress.

The nonenveloped avian reoviruses represent a distinct antigenic subgroup of orthoreoviruses. Unlike their mammalian counterparts, the avian reoviruses exhibit the unusual property of inducing rapid and extensive syncytium formation in cell cultures, a cytopathic effect more commonly associated with enveloped virus replication. While the syncytium-inducing capability of avian reovirus has been known for quite some time, the relationship between cell fusion and the virus replication cycle has not been determined. The conservation of the syncytial phenotype among all field isolates of avian reovirus suggests that avian reovirus-induced syncytium formation either reflects an essential step in the virus replication cycle involving intracellular membrane interactions or that cell fusion contributes to enhanced virus replication in infected animals. In order to distinguish between these possibilities, we have examined several aspects of virus replication in the presence of inhibitors of syncytium formation. Inhibitors of intracellular vesicle transport and O-linked glycosylation eliminated or markedly reduced syncytium formation with little effect on the rate or extent of virus macromolecular synthesis and infectious progeny virus production. Moreover, syncytium formation was not required for virus-induced cytopathology or virus egress but did significantly enhance the rate of both of these processes. The data indicate that, unlike the syncytium-inducing enveloped viruses, the membrane interactions and protein trafficking required for avian reovirus-induced syncytium formation do not reflect the sequelae of an essential step in the virus replication cycle. These results suggest that the conservation of the avian reovirus syncytial phenotype may reflect a fortuitous aspect of virus replication which confers advantages associated with the rapid spread of the virus within an infected host.

Animals↗
PubMed1993

Two neurotropic viruses, herpes simplex virus type 1 and mouse hepatitis virus, spread along different neural pathways from the main olfactory bulb.

Several neurotropic viruses enter the brain after peripheral inoculation and spread transneuronally along pathways known to be connected to the initial site of entry. In this study, the pathways utilized by two such viruses, herpes simplex virus type 1 and mouse hepatitis virus strain JHM, were compared using in situ hybridization following inoculation into either the nasal cavity or the main olfactory bulb of the mouse. The results indicate that both viruses spread to infect a unique and only partially overlapping set of connections of the main olfactory bulb. Both quantitative and qualitative differences were observed in the patterns of infection of known primary and secondary main olfactory bulb connections. Using immunohistochemistry for tyrosine hydroxylase combined with in situ hybridization, it was shown that only herpes simplex virus infected noradrenergic neurons in the locus coeruleus. In contrast, both viruses infected dopaminergic neurons in the ventral tegmental area, although mouse hepatitis virus produced a more widespread infection in the A10 group, as well as infecting A8 and A9. The results suggest that differential virus uptake in specific neurotransmitter systems contributes to the pattern of viral spread, although other factors, such as differences in access to particular synapses on infected cells and differences in the distribution of the cellular receptor for the two viruses, are also likely to be important. The data show that neural tracing with different viruses may define unique neural pathways from a site of inoculation. The data also demonstrate that two viruses can enter the brain via the olfactory system and localize to different structures, suggesting that neurological diseases involving disparate regions of the brain could be caused by different viruses, even if entry occurred at a common site.

Animals↗
PubMed1974

Evidence that the AKR murine-leukemia-virus genome is complete in DNA of the high-virus AKR mouse and incomplete in the DNA of the "virus-negative" NIH mouse.

The AKR mouse has a high titer of murine leukemia virus early in life, and virus-negative cells derived from embryos of this mouse strain can be activated to yield murine leukemia virus by treatment with 5-iododeoxyuridine. In contrast to this high-virus strain, the NIH Swiss mouse has a low incidence of leukemia and no murine leukemia virus has been isolated from it (virus-negative). We have investigated this difference between AKR and NIH mice by examining the sequences specific for murine leukemia virus in nucleic acids of these mice. A single-stranded viral-DNA probe synthesized in vitro using murine-leukemia-virus from the AKR mouse contains at least 87% of the sequences present in the 70S viral RNA; most of these sequences are in proportions similar to their content in the 70S RNA. Using this probe in nucleic acid hybridization experiments, we have shown that NIH-mouse-cell DNA and AKR-mouse-cell DNA differ with respect to sequences specific for AKR murine-leukemia-virus: NIH-mouse-cell DNA lacks some of the virus-specific sequences present in AKR-mouse-cell DNA, and there are two distinct sets of virus-specific sequences in AKR-mouse-cell DNA, whereas there is only one set in NIH-mouse-cell DNA.RNA from virus-negative AKR-mouse cells grown in tissue culture contains some, but not all, virus-specific RNA sequences; however, within 48 hr after initiating treatment of these cells with 5-iododeoxyuridine, the complete viral genome is represented in cellular RNA.

Animals↗
PubMed2000

Recovery and characterization of a chimeric rinderpest virus with the glycoproteins of peste-des-petits-ruminants virus: homologous F and H proteins are required for virus viability.

Rinderpest (RP) and peste-des-petits-ruminants (PPR) are two important diseases of domestic ruminants. To improve on currently available vaccines against PPR, we have created cDNA copies of the RP virus genome in which either the fusion (F) or hemagglutinin (H) gene, or both, was replaced with the corresponding gene from PPR virus. It was necessary to develop a modified rescue system in which the T7 RNA polymerase was provided by a recombinant fowlpox virus and the entire rescue procedure took place in Vero cells before we could obtain live virus from these chimeric constructs. No virus was recovered when only one of the glycoprotein genes was changed, but a chimeric virus containing both F and H genes from PPR virus was reproducibly rescued from cDNA, indicating that a virus-specific functional interaction takes place between the F and H proteins. The rescued virus expressing the PPR glycoproteins grew more slowly in tissue culture than either parental virus and formed abnormally large syncytia. Goats infected with the chimera showed no adverse reaction, as assessed by clinical signs, temperature, leukocyte count, virus isolation, and serology, and were protected from subsequent challenge with wild-type PPR virus.

Animals↗