martes, 27 de noviembre de 2012

Nonprimate Hepaciviruses in Domestic Horses, United Kingdom - - Emerging Infectious Disease journal - CDC

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Nonprimate Hepaciviruses in Domestic Horses, United Kingdom - - Emerging Infectious Disease journal - CDC


Nonprimate Hepaciviruses in Domestic Horses, United Kingdom

Sinéad Lyons, Amit Kapoor, Colin Sharp, Bradley S. Schneider, Nathan D. Wolfe, Geoff Culshaw, Brendan Corcoran, Bruce C. McGorum, and Peter SimmondsComments to Author 
Author affiliations: Author affiliations: University of Edinburgh, Edinburgh, Scotland, UK (S. Lyons, C. Sharp, G. Culshaw, B. Corcoran, B.C. McGorum, P. Simmonds); Columbia University, New York, New York, USA (A. Kapoor); Global Viral Forecasting Initiative, San Francisco, California, USA (B.S. Schneider, N.D. Wolfe)
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Although the origin of hepatitis C virus infections in humans remains undetermined, a close homolog of this virus, termed canine hepacivirus (CHV) and found in respiratory secretions of dogs, provides evidence for a wider distribution of hepaciviruses in mammals. We determined frequencies of active infection among dogs and other mammals in the United Kingdom. Samples from dogs (46 respiratory, 99 plasma, 45 autopsy samples) were CHV negative by PCR. Screening of 362 samples from cats, horses, donkeys, rodents, and pigs identified 3 (2%) positive samples from 142 horses. These samples were genetically divergent from CHV and nonprimate hepaciviruses that horses were infected with during 2012 in New York state, USA. Investigation of infected horses demonstrated nonprimate hepacivirus persistence, high viral loads in plasma (105–107 RNA copies/mL), and liver function test results usually within reference ranges, although several values ranged from high normal to mildly elevated. Disease associations and host range of nonprimate hepaciviruses warrant further investigation.
Hepatitis C virus (HCV) is a positive-sense RNA virus, classified as the type member of the family Flaviviridae and the genus Hepacivirus. HCV is a major human pathogen, causing persistent infections that target and eventually destroy the liver in a substantial proportion of those infected (1,2). HCV infections are distributed worldwide and have spread epidemically within the past 40–60 years within western countries through blood-borne routes such as blood and blood product transfusion and injection drug use.
HCV shows considerable genetic diversity; 7 genotypes show >30% nt sequence divergence from each other (3). Several of these genotypes are associated with suspected endemic source areas in central and western sub-Saharan Africa (genotypes 1, 2, and 4) (47) and Southeast Asia (genotypes 3 and 6) (8,9). These regions harbor the greatest diversity of HCV subtypes, implying a long-term, endemic circulation of the virus for several hundred years. The spread of certain genotype variants from these populations, such as 1a and 1b to Western countries, 3a among injection drug users in Europe, and 4a to Egypt, where it was extensively transmitted by medical injections (1014), show several parallels with the emergence and rapid spread of HIV-1 among new risk groups from a central African reservoir over a similar time frame (15).
Based on this model, it has been frequently speculated that HCV could have an ultimate animal origin in >1 nonhuman primate species, in much the same way as human HIV-1 originated from chimpanzees (15). Three of the Pan troglodytes chimpanzee subspecies are frequently infected in the wild with a lentivirus that ultimately was derived from simian immunodeficiency viruses infecting Old World monkey species (16). The hypothesis for an equivalent nonhuman primate origin for HCV fueled several published (17,18) and unpublished (S. Lyons et al., unpub. data) surveys for HCV or HCV-like viruses in chimpanzees, other apes, and a variety of Old World monkey species (19). These studies were encouraged by the serendipitous detection of a virus distantly related to HCV, termed GB virus B (GBV-B), in a laboratory-housed tamarin, a New World monkey (20,21). This detection was speculated to represent, in evolutionarily terms, the New World monkey homolog of HCV, a scenario that supports the possibility for the widespread distribution of further HCV-like viruses among Old World monkey species in Africa and Asia. Despite the plausibility of this hypothesis, we found that no survey to date has detected or obtained serologic evidence for infection with HCV or HCV-like viruses in any ape or Old World monkey species screened in published data (17,18) or in the aforementioned unpublished data of Lyons et al. As a further puzzling observation, GBV-B infection has not been reported in any other tamarin or other New World monkey species either in the wild or among captive animals. Like HCV, its origin remains unknown.
Considering this background and previous focus on primates for HCV origins, it came as a complete surprise that a virus, much more closely related to HCV than GBV-B, was recently described for domestic dogs (22). Its host and apparent tropism for the respiratory tract (and potential association with infectious respiratory disease) represent major differences from what might be expected for a close relative of HCV. It came as a further surprise that CHV RNA sequences were detected in plasma samples from 8 of 103 horses in New York state, USA (23). Results of a novel serologic test of samples from horses for antibodies to the conserved nonstructural protein 3 (NS3) showed an overall seropositivity of 35%, and 80 samples from dogs were negative by serologic testing and PCR. The wider host range of the virus implied by these findings led the authors to propose a new name, non-primate hepacivirus (NPHV) for CHV, and this new nomenclature is used in the current study.
To investigate the species distribution of NPHV or homologs in a range of mammalian species and to investigate clinical features of infection, we initiated large-scale PCR–based screening of plasma, respiratory, and postmortem liver, spleen, and lung samples from horses, dogs, cats, and other species originating in the United Kingdom. The PCR was specific for conserved sequences in the 5′ untranslated region (5′-UTR) and the NS3 regions of NPHV. NPHV was detected in 3 horses (horse 1, horse 2, and horse 3); initial characterization of the epidemiology and clinical features of NPHV infections were performed and compared with those of HCV.

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