Biomedical subjects

M Gerard O'Sullivan

Publications and source records attributed to M Gerard O'Sullivan.

5 recordsLinked to original sources

PubMed2006

Simian parvovirus infection in cynomolgus monkey heart transplant recipients causes death related to severe anemia.

BACKGROUND: Simian parvovirus (SPV) was first isolated from cynomolgus monkeys. Like human parvovirus B19, this virus has a predilection for erythroid cells. During acute SPV infection, clinical signs are usually mild or inapparent, but severe anemia may occur in immunocompromised animals. We report several cases of symptomatic SPV infection in cynomolgus monkeys following heart transplantation. METHODS: Twenty-three consecutive abdominal heterotopic heart transplants were studied. Viremia, measured by dot blot and/or PCR, and SPV-specific antibodies were determined retrospectively. RESULTS: All except one animal were on an immunosuppressive protocol. In all, 48% (11/23) of transplant recipients had viremia with SPV detected at some point after transplant. An additional 22% seroconverted before or after transplant, and were asymptomatic without detectable SPV. Of the 11 acutely viremic animals, five were euthanized because of severe anemia attributed to SPV. The remaining 30% of the transplant recipients did not seroconvert and were asymptomatic. Of seven recipients of donor tissue from seropositive or viremic animals, five became viremic and three died with anemia. No immunosuppressive regimen was implicated in increased susceptibility; the one transplant recipient not treated with immunosuppressive agents died with anemia and acute viremia two weeks after explant of a rejected graft. CONCLUSION: SPV is an important pathogen in surgically manipulated cynomolgus monkeys, particularly with immune compromise. Once introduced into a colony, clinically silent SPV infection could be readily transmitted within the environment. Transmission and disease occur at high frequency with an organ from a PCR-negative, seropositive donor, suggesting that latent virus can be conveyed by the organ.

Anemia↗

PubMed2004

Simian parvovirus infection: a potential zoonosis.

INTRODUCTION: Simian parvovirus (SPV) causes severe anemia in immunocompromised macaques. The closely related erythrovirus, parvovirus B19, causes anemia in susceptible humans and can be grown in human bone marrow mononuclear cells in vitro. We hypothesized that SPV may infect humans and replicate in human bone marrow mononuclear cells. METHODS: Serum samples from handlers of an SPV-seropositive macaque colony were tested by Western blot for evidence of antibodies to SPV. SPV capsid protein was expressed in insect cells, and SPV was cultured in human and macaque bone marrow mononuclear cells. RESULTS: Fifty-one percent of exposed handlers (n=65) were found to be SPV seropositive, compared with 35% of nonexposed individuals (n=124). In 17% of exposed handlers, compared with 6% of nonexposed individuals, antibodies were directed to SPV but not to B19. SPV capsid proteins, like those of B19, self-assembled to form parvovirus-like particles, and these capsids, like B19 capsids, bound to globoside, suggesting that globoside is also the receptor for SPV. We demonstrated that SPV could replicate in vitro in both human and macaque bone marrow mononuclear cells and that it was cytotoxic to erythroid progenitor cells. CONCLUSIONS: Our data suggest that SPV may infect human bone marrow mononuclear cells in vitro and in vivo and should be considered a potential zoonosis.

Animals↗

PubMed2004

Revised guides for organ sampling and trimming in rats and mice--Part 2. A joint publication of the RITA and NACAD groups.

This is the second part of a series of three articles on trimming instructions of rat and mouse protocol organs and tissues in regulatory type toxicity studies, covering the respiratory, male and female genital, and the endocrine systems. The article is based on the experience of the European RITA and American NACAD working groups and is an extended revision of trimming guides published in 1995 (Bahnemann et al.). The optimum localization for tissue preparation, the sample size, the direction of sectioning and the number of sections to be prepared is described organ by organ. These descriptions are illustrated for each organ by a schematic drawing and/or a macro-photograph showing the plane of section as well as a low magnification of the H&E stained slide demonstrating the optimum "end-product". The objectives of this work, as addressed in detail in the first part (Ruehl-Fehlert et al. 2003), are to standardize tissue sampling and trimming, to improve the comparability of historical data obtained from different studies and different laboratories, ensure the presence of all relevant target sites for histopathological evaluation and provide technical advice for preparatory techniques during necropsy, fixation and trimming. dardize tissue sampling and trimming, to improve the comparability of historical data obtained from different studies and different laboratories, ensure the presence of all relevant target sites for histopathological evaluation and provide technical advice for preparatory techniques during necropsy, fixation and trimming.

Animals↗

PubMed2004

Splice junction map of simian parvovirus transcripts.

The transcription map of simian parvovirus (SPV), an Erythrovirus similar to Parvovirus B19, was investigated. RNA was extracted from tissues of experimentally infected cynomolgus macaques and subjected to reverse transcription-PCR with SPV-specific primers. The PCR products were cloned and sequenced to identify splice junctions. A total of 14 distinct sequences were identified as putative partial transcripts. Of these, 13 were spliced; a single unspliced transcript putatively encoded NS1. Sequence analysis revealed that spliced partial transcripts may encode portions of open reading frames for the major capsid proteins VP1 and VP2 and smaller, unknown proteins. These unspliced and spliced transcripts and putative proteins encoded by SPV were similar to those of B19. Initial splice junctions at nucleotides 279 and 333 were analogous to those at nucleotides 406 and 441, respectively, in B19. Seven of the 10 splices identified had typical GT/AG donor/acceptor junctions. The splice sites were confirmed by Northern blotting and autoradiography. In contrast to B19, which has a maximum of two splices per transcript, up to three splices were observed in SPV transcripts. A spliced transcript putatively encoding a truncated version of NS1, as seen with minute virus of mice and adeno-associated virus 2, was also observed. The findings indicate that that the splicing pattern of transcripts of SPV and B19 is similar, but SPV also has coding strategies in common with other parvoviruses.

Animals↗

PubMed2004

Comparison of the transcription profile of simian parvovirus with that of the human erythrovirus B19 reveals a number of unique features.

Simian parvovirus (SPV) is a member of the genus Erythrovirus and is closely related to the human parvovirus B19. Natural and experimental infection of monkeys with SPV resembles B19 infection of human. We report a detailed characterization of the viral RNAs and proteins generated following transfection of cloned SPV into COS cells and SPV infection of the human erythroid progenitor line UT-7/Epo-S1. SPV and B19 are 50% identical at the nucleotide level, and although their basic transcription and protein expression profiles were generally similar, there were also significant differences. SPV pre-mRNAs contain three introns, compared to two found for B19: an additional intron was found within the capsid-coding region. RNAs in which this intron was spliced were abundant and encoded the SPV 14-kDa protein (analogous to the B19 11-kDa protein), which initiated at an AUG in the exon preceding the third intron. Unlike B19, SPV RNAs were also spliced between the donor of the first intron and the acceptor of the second intron. The third intron was additionally spliced from a portion of these molecules; these mRNAs encoded the 14-kDa protein. A portion was not spliced further and encoded VP2. Like B19, SPV has a polyadenylation signal [AAUAAA (pA)p] in the middle of the genome, which directed efficient polyadenylation of both spliced and unspliced mRNAs (encoding a putative 10-kDa protein, analogous to the B19 7.5-kDa protein, and SPV NS1, respectively). The 14-kDa protein was localized to both in the nucleus and cytoplasm.

Animals↗