Microbial safety in xenotransplantation

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Abstract

As clinical trials are in progress involving porcine islet cell transplantation, microbial safety remains a key issue. Therefore, in the context of pig-to-human xenotransplantation, we provide an overview of the recent progress in the studies of relevant viruses including well known problematic viruses, such as herpesviruses and porcine endogenous retroviruses (PERV) in addition to some emerging issues regarding other pathogens. The ability of herpesvirus to infect across species barriers is probably underestimated and requires monitoring and control of both xenograft donors and recipients for latent infection. Exclusion from donors and recipient monitoring for other exogenous pathogens including newly identified Parvovirus-4 are warranted. The availability of the swine whole genome sequence may help to characterize and select donor animals with less PERV infectivity. Rigorous PERV monitoring in both clinical and preclinical xenotransplantation experiments must be included in clinical protocols. A wide range of pathogens, both viruses and bacteria, pose potential safety problems in xenotransplantation, highlighting the importance of prescreening of the donor animals, and careful monitoring and follow-up of the patients.

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Human Bocaviruses Are Highly Diverse, Dispersed, Recombination Prone, and Prevalent in Enteric Infections

Amit Kapoor, Peter Simmonds, Elizabeth Slikas … (2010)

Abstract A new species of parvovirus, tentatively named human bocavirus 4 (HBoV4), was genetically characterized. Among 641 feces samples obtained from children and adults, the most commonly detected bocavirus species were, in descending order, HBoV2, HBoV3, HBoV4, and HBoV1, with an HBoV2 prevalence of 21% and 26% in Nigerian and Tunisian children, respectively. HBoV3 or HBoV4 species were found in 12 of 192 patients with non-polio acute flaccid paralysis in Tunisia and Nigeria and 0 of 96 healthy Tunisian contacts (P= .01). Evidence of extensive recombination at the NP1 and VP1 gene boundary between and within bocavirus species was found. The high degree of genetic diversity seen among the human bocaviruses found in feces specimens, relative to the highly homogeneous HBoV1, suggest that this worldwide-distributed respiratory pathogen may have recently evolved from an enteric bocavirus after acquiring an expanded tropism favoring the respiratory tract. Elucidating the possible role of the newly identified enteric bocaviruses in human diseases, including acute flaccid paralysis and diarrhea, will require further epidemiological studies.

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Multiple diverse circoviruses infect farm animals and are commonly found in human and chimpanzee feces.

Barbara C. N. Müller, H Triki, Jean-Bosco Ndjango … (2010)

Circoviruses are known to infect birds and pigs and can cause a wide range of severe symptoms with significant economic impact. Using viral metagenomics, we identified circovirus-like DNA sequences and characterized 15 circular viral DNA genomes in stool samples from humans in Pakistan, Nigeria, Tunisia, and the United States and from wild chimpanzees. Distinct genomic features and phylogenetic analysis indicate that some viral genomes were part of a previously unrecognized genus in the Circoviridae family we tentatively named "Cyclovirus" whose genetic diversity is comparable to that of all the known species in the Circovirus genus. Circoviridae detection in the stools of U.S. adults was limited to porcine circoviruses which were also found in most U.S. pork products. To determine whether the divergent cycloviruses found in non-U.S. human stools were of dietary origin, we genetically compared them to the cycloviruses in muscle tissue samples of commonly eaten farm animals in Pakistan and Nigeria. Limited genetic overlap between cycloviruses in human stool samples and local cow, goat, sheep, camel, and chicken meat samples indicated that the majority of the 25 Cyclovirus species identified might be human viruses. We show that the genetic diversity of small circular DNA viral genomes in various mammals, including humans, is significantly larger than previously recognized, and frequent exposure through meat consumption and contact with animal or human feces provides ample opportunities for cyclovirus transmission. Determining the role of cycloviruses, found in 7 to 17% of non-U.S. human stools and 3 to 55% of non-U.S. meat samples tested, in both human and animal diseases is now facilitated by knowledge of their genomes.

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Hepatitis E virus and chronic hepatitis in organ-transplant recipients.

Jean-Michel Mansuy, Nathalie Danjoux, Florence Abravanel … (2008)

Hepatitis E virus (HEV) is considered an agent responsible for acute hepatitis that does not progress to chronic hepatitis. We identified 14 cases of acute HEV infection in three patients receiving liver transplants, nine receiving kidney transplants, and two receiving kidney and pancreas transplants. All patients were positive for serum HEV RNA. Chronic hepatitis developed in eight patients, as confirmed by persistently elevated aminotransferase levels, serum HEV RNA, and histologic features of chronic hepatitis. The time from transplantation to diagnosis was significantly shorter and the total counts of lymphocytes and of CD2, CD3, and CD4 T cells were significantly lower in patients in whom chronic disease developed. Copyright 2008 Massachusetts Medical Society.