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At least 19 recordsLinked to original sources
PubMed2004

Different susceptibility of B19 virus and mice minute virus to low pH treatment.

BACKGROUND: Parvoviridae are small nonenveloped viruses that are known to be highly resistant to physico-chemical treatments. Because low pH is frequently applied to process intermediates or final products, the impact of such conditions on the human erythrovirus B19 (B19V) and the mouse parvovirus (mice minute virus, MMV) was assessed, which is often used as a model for B19V. Owing to the lack of a suitable cultivation and/or detection system for B19V no such data exist so far. STUDY DESIGN AND METHODS: Virus inactivation was monitored by decrease of infectivity and loss of capsid integrity. Infectious B19V was quantified by detection of virus-specific messenger RNA from Ku812Ep6 cells. To measure capsid integrity, endonucleases were added after exposure to low pH and the encapsidated (endonuclease-protected) virus DNA was quantified by real-time PCR. RESULTS: B19V was inactivated greater than 5 log after 2 hours at pH 4, whereas MMV was resistant over 9 hours. Infectivity data strongly correlated with data obtained by the endonuclease assay. Capsid disintegration was observed in immunoglobulin G as well as in different albumin solutions. Temperature and pH showed concerted impact on B19V capsid disintegration. CONCLUSION: Our data show that B19V is much more vulnerable toward low pH conditions than MMV. Together with the previously reported susceptibility of B19V toward wet heat conditions, low pH is the second treatment where erythrovirus B19V is less resistant than viruses from the parvovirus genus.

Animals↗
PubMed2004

The ubiquitin-proteasome machinery is essential for nuclear translocation of incoming minute virus of mice.

Minute virus of mice (MVM) infection is disrupted by proteasome inhibitors. Here, we show that inhibition of the ubiquitin-proteasome pathway did not affect viral entry and had influence neither on the natural proteolytic cleavage of VP2 to VP3 nor on the externalization of the N terminal of VP1. In both MG132-treated and untreated cells, MVM particles accumulated progressively in the perinuclear region. However, in MG132-treated cells, MVM was not able to penetrate into the nuclei, remaining blocked in the perinuclear region without capsid disassembly. MVM was similarly sensitive to MG132 in the two cell lines tested, A9 and NB324K. After releasing from the reversible MG132 block, MVM recovered the ability to translocate to the nuclei and replicate. Analysis of viral capsid proteins during internalization showed no evidence of capsid ubiquitination or degradation. We examined the effect of MG132 on two other parvoviruses, canine (CPV) and bovine parvovirus (BPV). Similarly to MVM, CPV infection was sensitive to MG132; however, BPV infection, as previously shown for adeno-associated viruses (AAVs), was not disturbed. These findings suggest that parvoviruses follow divergent strategies for nuclear transport, some of them requiring active proteasomes.

Active Transport, Cell Nucleus↗
PubMed2006

Exploring the contribution of distal P4 promoter elements to the oncoselectivity of Minute Virus of Mice.

Minute Virus of Mice (MVM) shares inherent oncotropic properties with other members of the genus Parvovirus. Two elements responsible, at least in part, for this oncoselectivity have been mapped to an Ets1 binding site adjacent to the P4 TATA box of the initiating promoter, P4, and to a more distal cyclic AMP responsive element (CRE), located within the telomeric hairpin stem. Here the CRE overlaps one half-site for the binding of parvoviral initiation factor (PIF), which is essential for viral DNA replication. We used a degenerate oligonucleotide selection approach to show that CRE binding protein (CREB) selects the sequence ACGTCAC within this context, rather than its more generally accepted palindromic TGACGTCA recognition site. We have developed strategies for manipulating these sequences directly within the left-end palindrome of the MVM infectious clone and used them to clone mutants whose CRE either matches the symmetric consensus sequence or is scrambled, or in which the PIF binding site is incrementally weakened with respect to the CRE. The panel of mutants were tested for fitness relative to wildtype in normal murine fibroblasts A9 or transformed human fibroblasts 324 K, through multiple rounds of growth in co-infected cultures, using a differential real-time quantitative PCR assay. We confirmed that inactivating the CRE substantially abrogates oncoselectivity, but found that improving its fit to the palindromic consensus is somewhat debilitating in either cell type. We also confirmed that reducing the PIF half-site spacing by one basepair enhances oncoselectivity, but found that a further basepair deletion significantly reduces this effect.

Animals↗
PubMed2002

Serodiagnosis of mice minute virus and mouse parvovirus infections in mice by enzyme-linked immunosorbent assay with baculovirus-expressed recombinant VP2 proteins.

Mice minute virus (MMV) and mouse parvovirus (MPV) type 1 are the two parvoviruses known to naturally infect laboratory mice and are among the most prevalent infectious agents found in contemporary laboratory mouse colonies. Serologic assays are commonly used to diagnose MMV and MPV infections in laboratory mice; however, highly accurate, high-throughput serologic assays for the detection of MMV- and MPV-infected mice are needed. To this end, the major capsid viral protein (VP2) genes of MMV and MPV were cloned and MMV recombinant VP2 (rVP2) and MPV rVP2 proteins were expressed by using a baculovirus system. MMV rVP2 and MPV rVP2 spontaneously formed virus-like particles that were morphologically similar to empty parvovirus capsids. These proteins were used as antigens in enzyme-linked immunosorbent assays (ELISAs) to detect anti-MMV or anti-MPV antibodies in the sera of infected mice. Sera from mice experimentally infected with MMV (n = 43) or MPV (n = 35) and sera from uninfected mice (n = 30) were used to evaluate the ELISAs. The MMV ELISA was 100% sensitive and 100% specific in detecting MMV-infected mice, and the MPV ELISA was 100% sensitive and 98.6% specific in detecting MPV-infected mice. Both assays outperformed a parvovirus ELISA that uses a recombinant nonstructural protein (NS1) of MMV as antigen. The MMV rVP2 and MPV rVP2 proteins provide a ready source of easily produced antigen, and the ELISAs developed provide highly accurate, high-throughput assays for the serodiagnosis of MMV and MPV infections in laboratory mice.

Animals↗
PubMed2006

Antemortem detection of mouse parvovirus and mice minute virus by polymerase chain reaction (PCR) of faecal samples.

Parvoviruses remain one of the most common viral infections seen in laboratory mouse colonies. The purpose of this study was to develop an antemortem polymerase chain reaction (PCR) assay to detect mice infected with mouse parvovirus-1 (MPV) and mice minute virus (MMV) using faecal samples. The MMV PCR assay consistently detected as few as 100 plasmid copies of MMV in faecal samples, while the MPV PCR assay detected as few as 10 plasmid copies of MPV. Faecal pellets from infected mice held at room temperature from 1 to 7 days tested positive by MMV and MPV PCR, respectively. This demonstrates that parvovirus DNA is stable in faecal samples kept at room temperature. PCR assays were also used to follow the length of MMV and MPV shedding in faeces from SENCAR mice, which were endemically infected with multiple agents. MMV faecal shedding was detected in 60-70% of the mice 5-7 weeks old, and by 13 weeks of age, faecal samples from all mice were negative for MMV. MPV faecal shedding was detected in 90-100% of the mice 5-11 weeks old; however, by 19 weeks of age, faecal samples from all mice were negative for MPV. These findings confirm that faecal shedding occurs for a limited time and suggest that 5-9-week-old mice are the most appropriate age group in endemically infected mice for faecal testing by MMV and MPV PCR.

Animals↗
PubMed1986

Suppression of Ehrlich ascites tumors in mice by minute virus of mice.

As a model system to study parvoviral oncosuppression, Ehrlich ascites (EA) cells were injected into the peritoneal cavities of ICR mice, and the effect of im injection of minute virus of mice (MVM) on EA tumor growth was examined. Coinjection with MVM resulted in a dramatic inhibition of EA tumor formation. Tumor suppression required viable, infectious virus. Mice that had survived one EA-MVM coinjection acquired long-term resistance to additional injections of EA cells.

Animals↗
PubMed2004

Increased levels of B1 and B2 SINE transcripts in mouse fibroblast cells due to minute virus of mice infection.

Minute virus of mice (MVM), an autonomous parvovirus, has served as a model for understanding parvovirus infection including host cell response to infection. In this paper, we report the effect of MVM infection on host cell gene expression in mouse fibroblast cells (LA9 cells), analyzed by differential display. Somewhat surprisingly, our data reveal that few cellular protein-coding genes appear to be up- or downregulated and identify the murine B1 and B2 short interspersed element (SINE) transcripts as being increased upon MVM infection. Primer extension assays confirm the effect of MVM infection on SINE expression and demonstrate that both SINEs are upregulated in a roughly linear fashion throughout MVM infection. They also demonstrate that the SINE response was due to RNA polymerase III transcription and not contaminating DNA or RNA polymerase II transcription. Furthermore, expression of MVM NS1, the major nonstructural protein, by transient transfection also leads to an increase in both murine SINEs. We believe this is the first time that the B1 and B2 SINEs have been shown to be altered by viral infection and the first time parvovirus infection has been shown to increase SINE expression. The increase in SINE transcripts caused by MVM infection does not appear to be due to an increase in either of the basal transcription factors TFIIIC110 or 220, in contrast to that which has been shown for other viruses.

Animals↗
PubMed1998

An Sp1-binding site and TATA element are sufficient to support full transactivation by proximally bound NS1 protein of minute virus of mice.

The minute virus of mice (MVM) P38 Sp1-binding site and TATA box, inserted in an otherwise heterologous plasmid background, could be transactivated to high levels by the MVM NS1 protein targeted proximally to these sequences, demonstrating that these core promoter regulatory elements are sufficient to support essentially wild-type levels of NS1-transactivated expression and suggesting that NS1 may act directly or indirectly with Sp1 and or elements of the general transcription machinery. Accordingly, we show that bacterially generated NS1 can interact strongly, independent of nucleic acid bridging, and most likely directly with Sp1 in vitro and can associate, in a nucleic acid-independent manner, with endogenous Sp1 as it exists in a complex transcriptionally active murine nuclear extract NS1 achieves the same fold activation of an isolated TATA element over its low basal level and can also be demonstrated to interact efficiently and specifically with the general transcription factors TBP and TFIIA (alpha, beta) in vitro.

Animals↗
PubMed1996

The effect of regulatory sequence elements upon the initiation of DNA replication of the minute virus of mice.

The minute virus of mice (MVM) genome is a linear single-stranded length of approximately 5000 nucleotides of DNA with unique terminal palindromic sequences at both ends. The left(3') hairpin is used to prime the initiation of DNA synthesis on parental single-strand DNA while the right (5') hairpin or stem-plus-arms structure can also prime the initiation of DNA synthesis during synthesis of dimer and higher oligomers as well as synthesis of progeny single strands. Previous studies have shown that if viral duplex DNA was input into an in vitro DNA replication system using extracts from uninfected HeLa cells, the 5' end of the molecule was able to form a hairpin and initiate DNA synthesis by DNA polymerase delta (Cossons et al. (1996), Virology 216, 258-264). In this study, the effect of the deletion of known cis-acting genetic elements upon the initiation of DNA replication was studied using a series of MVM mutants with deletions within the 5' terminal region. Mutants containing deletions of elements A (nucleotides 4489-4636), B (nucleotides 4636-4695), and either one or both of the 65-bp repeats (nucleotides 4720-4785 and 4785-4849) were used as template in the in vitro DNA replication system. When element A was deleted, the efficiency of initiation decreased significantly. Subsequent removal of element B, leaving just the two 65-bp repeats, restored levels of initiation back to those seen in the wild-type genome. In the absence of either A or B both 65-bp repeats were necessary for efficient initiation, and removal of one of these repeats caused a decrease in efficiency. Thus, element B appeared to have a negative regulatory effect (in the absence of element A), and element A appeared to have a positive regulatory effect, at least in the presence of element B. These data demonstrate, for the first time, a complex interaction between these cis-acting regulatory elements which can function as both positive or negative regulators in the initiation of MVM DNA replication.

Animals↗
PubMed1999

Neoplastic transformation-associated stimulation of the in vitro resolution of concatemer junction fragments from minute virus of mice DNA.

Minute virus of mice (MVM) shows an oncotropic behavior reflected by its ability to amplify its genome more efficiently in a number of transformed versus normal cells. In vivo and in vitro studies revealed that the major effect of cell transformation on MVM DNA replication occurs at the level of double-stranded replicative-form amplification. In particular, resolution of MVM DNA concatemers into monomers was found to be highly sensitive to neoplastic transformation.

Cell Transformation, Neoplastic↗
PubMed1998

Functional implications of the structure of the murine parvovirus, minute virus of mice.

BACKGROUND: Minute virus of mice (MVM) is a single-stranded (ss) DNA-containing, murine parvovirus with a capsid built up of 60 icosahedrally related polypeptide chains, each of which consists of the C-terminal region common to two structural proteins, VP1 and VP2. In infectious virions, most VP2 molecules are cleaved to VP3 by the removal of about 20 amino acids from the N terminus. Of the 587 amino acids in VP2, approximately half are identical to those in the analogous capsid protein of the antigenically distinct canine parvovirus (CPV), the crystal structure of which has previously been determined. The three-dimensional structure determination of MVMi (the immunosuppressive strain of MVM) was previously reported to 3.5 A resolution. RESULTS: We report here an analysis of the MVMi virus structure and provide insights into tissue tropism, antigenicity and DNA packaging. Amino acids determining MVM tissue tropism were found to cluster on, or near, the viral surface. A conserved, glycine-rich, N-terminal peptide was seen to run through a cylindrical channel along each fivefold axis and may have implications for antigenicity. Density within the virion was interpreted as 29 ssDNA nucleotides per icosahedral asymmetric unit, and accounts for over one-third of the viral genome. CONCLUSIONS: The presence of the glycine-rich sequence in the fivefold channels of MVMi provides a possible mechanism to explain how the unique N-terminal region of VP1 becomes externalized in infectious parvovirions. Residues that determine tropism may form an attachment recognition site for a secondary host-cell factor that modulates tissue specificity. The ordering of nucleotides in a similar region of the interior surface in the CPV and MVMi capsids suggests the existence of a genomic DNA-recognition site within the parvoviral capsid.

Amino Acid Sequence↗
PubMed1999

Severe leukopenia and dysregulated erythropoiesis in SCID mice persistently infected with the parvovirus minute virus of mice.

Parvovirus minute virus of mice strain i (MVMi) infects committed granulocyte-macrophage CFU and erythroid burst-forming unit (CFU-GM and BFU-E, respectively) and pluripotent (CFU-S) mouse hematopoietic progenitors in vitro. To study the effects of MVMi infection on mouse hemopoiesis in the absence of a specific immune response, adult SCID mice were inoculated by the natural intranasal route of infection and monitored for hematopoietic and viral multiplication parameters. Infected animals developed a very severe viral-dose-dependent leukopenia by 30 days postinfection (d.p.i.) that led to death within 100 days, even though the number of circulating platelets and erythrocytes remained unaltered throughout the disease. In the bone marrow of every lethally inoculated mouse, a deep suppression of CFU-GM and BFU-E clonogenic progenitors occurring during the 20- to 35-d.p.i. interval corresponded with the maximal MVMi production, as determined by the accumulation of virus DNA replicative intermediates and the yield of infectious virus. Viral productive infection was limited to a small subset of primitive cells expressing the major replicative viral antigen (NS-1 protein), the numbers of which declined with the disease. However, the infection induced a sharp and lasting unbalance of the marrow hemopoiesis, denoted by a marked depletion of granulomacrophagic cells (GR-1(+) and MAC-1(+)) concomitant with a twofold absolute increase in erythroid cells (TER-119(+)). A stimulated definitive erythropoiesis in the infected mice was further evidenced by a 12-fold increase per femur of recognizable proerythroblasts, a quantitative apoptosis confined to uninfected TER-119(+) cells, as well as by a 4-fold elevation in the number of circulating reticulocytes. Therefore, MVMi targets and suppresses primitive hemopoietic progenitors leading to a very severe leukopenia, but compensatory mechanisms are mounted specifically by the erythroid lineage that maintain an effective erythropoiesis. The results show that infection of SCID mice with the parvovirus MVMi causes a novel dysregulation of murine hemopoiesis in vivo.

Animals↗
PubMed1977

Serologic study on the prevalence of murine viruses in five Canadian mouse colonies.

A serologic study was made of five Canadian mouse colonies to determine the prevalence of antibodies to 11 murine viruses. A total of 139 sera from the five colonies were evaluated by complement fixation or hemagglutination inhibition methods. Viral antibodies were present in all five colonies. Antibodies to pneumonia virus of mice, minute virus of mice, Theiler's encephalomyelitis virus, and reovirus type 3 were found in all five colonies. K-virus antibodies were present in four colonies. Polyoma virus antibodies were found in two colonies and Sendai virus antibodies in two other colonies. Mouse hepatitis virus antibodies were present at a low prevalence in three of the five colonies. No antibodies to adenovirus, lymphocytic choriomeningitis virus, and ectromelia were detected in any of the colonies.

Animals↗
PubMed1995

Myeloid depression follows infection of susceptible newborn mice with the parvovirus minute virus of mice (strain i).

The in vivo myelosuppressive capacity of strain i of the parovirus minute virus of mice (MVMi) was investigated in newborn BALB/c mice inoculated with a lethal intranasal dose. MVMi infection reached maximum levels of DNA synthesis and infectious titers in lymphohemopoietic organs at 4 to 6 days postinoculation and was restricted by an early neutralizing humoral immune response. After viral control (by 10 days postinoculation), a significant decrease in femoral and splenic cellularity, as well as in granulocyte-macrophage colony-forming unit and erythroid burst-forming unit hemopoietic progenitors, was observed in most inoculated animals. This delayed myeloid depression, although it may be not a major cause of the lethality of the infection, implies indirect pathogenic mechanisms induced by MVMi infection in a susceptible host.

Animals↗
PubMed1983

Response of weanling random-bred mice to inoculation with minute virus of mice.

Several methods (hemagglutination inhibition, immunofluorescence, enzyme-linked immunosorbent assay, and serum neutralization) for detection of serum antibody to minute virus of mice were compared using sera from random-bred, weanling mice experimentally inoculated by either the intraperitoneal or oral route. Antibody was detected by all methods in sera from intraperitoneally inoculated mice by 4 days post-inoculation, while sera from orally infected mice contained detectable antibody on day 7 by all methods except neutralization. Serum neutralizing antibody was detected much later and at lower levels in sera of orally infected mice than in sera of intraperitoneally inoculated mice. Virus was recovered from the intestines of both inoculation groups and from the kidneys of intraperitoneally inoculated mice. Among the latter animals, virus was still detectable 10 days post-inoculation, several days after serum neutralizing antibody had developed. Sentinel dams with litters placed in cages with intraperitoneally inoculated mice 10 days after the inoculation were seropositive by immunofluorescence and enzyme-linked immunosorbent assay when tested 3 weeks after contact.

Animals↗
PubMed1984

Expression of minute virus of mice structural proteins in murine cell lines transformed by bovine papillomavirus-minute virus of mice plasmid chimera.

Recombinant plasmids containing the genomes of both bovine papillomavirus type I and minute virus of mice (MVM) were constructed and used to transform mouse C127 cells. Transformed lines that express MVM gene products with high efficiency were isolated and characterized. These transformants synthesize large amounts of MVM structural polypeptides and spontaneously assemble them into empty virion particles that are released into the culture medium. These lines were, however, genetically unstable; they slowly generated subpopulations that failed to express MVM-specific proteins, and they possessed episomal DNA in which both MVM and bovine papillomavirus sequences were deleted or rearranged, or both. Clonal isolates of these transformants were also superinfectible by infectious MVM virus. Therefore, in spite of their instability, they should be useful host cell lines for transcomplementing mutations introduced into the MVM genome and for growing defective viruses as virions.

Animals↗
PubMed1996

DNA polymerase delta-dependent formation of a hairpin structure at the 5' terminal palindrome of the minute virus of mice genome.

The parvovirus the minute virus of mice (MVM) has a linear single-stranded DNA genome with unique palindromic sequences at both termini which enable it to fold back on itself and form hairpin or cruciform-type structures. The purpose of this study was to examine the primary events occurring during MVM replication mediated solely by the host cell replication machinery. In an in vitro DNA replication system using HeLa cell extracts, we found that there was a distinct activity that utilized the 5' terminal palindrome sequence of MVM to produce a secondary structure from a duplex extended form, in a time-dependent fashion. The secondary structure was due to the formation of a hairpin rather than a stem-plus-arms type structure and was associated with initiation of DNA synthesis, performed specifically by DNA polymerase delta. Inhibition of DNA polymerase alpha had no effect upon this activity. Removal of all but 13 base pairs of the hairpin arm abolished the synthesis of DNA, indicating that there is a minimal length requirement for the duplex region of DNA or that this region contains regulatory genetic elements. These data are consistent both with the role of DNA polymerase delta in extending the synthesis of DNA from a DNA primer and with unidirectional continuous DNA synthesis, initiating from a hairpin, as a mode of replication for MVM.

Animals↗
PubMed2005

Genome packaging sense is controlled by the efficiency of the nick site in the right-end replication origin of parvoviruses minute virus of mice and LuIII.

The parvovirus minute virus of mice (MVM) packages predominantly negative-sense single strands, while its close relative LuIII encapsidates strands of both polarities with equal efficiency. Using genomic chimeras and mutagenesis, we show that the ability to package positive strands maps not, as originally postulated, to divergent untranslated regions downstream of the capsid gene but to the viral hairpins and predominantly to the nick site of OriR, the right-end replication origin. In MVM, the sequence of this site is 5'-CTAT(black triangle down)TCA-3', while in LuIII a two-base insertion (underlined) changes it to 5'-CTATAT(black triangle down)TCA-3'. Matched LuIII genomes differing only at this position (designated LuIII and LuDelta2) packaged 47 and <8% positive-sense strands, respectively. OriR sequences from these viruses were both able to support NS1-mediated nicking in vitro, but initiation efficiency was consistently two- to threefold higher for LuDelta2 derivatives, suggesting that LuIII's ability to package positive strands is determined by a suboptimal right-end origin rather than by strand-specific packaging sequences. These observations support a mathematical "kinetic hairpin transfer" model, previously described by Chen and colleagues (K. C. Chen, J. J. Tyson, M. Lederman, E. R. Stout, and R. C. Bates, J. Mol. Biol. 208:283-296, 1989), that postulates that preferential excision of particular strands is solely responsible for packaging specificity. By analyzing replicative-form (RF) DNA generated in vivo during LuIII and LuDelta2 infections, we extend this model, showing that positive-sense strands do accumulate in LuDelta2 infections as part of duplex RF DNA, but these do not support packaging. However, replication is biphasic, so that accumulation of positive-sense strands is ultimately suppressed, probably because the onset of packaging removes newly displaced single strands from the replicating pool.

Animals↗