Investigation of porcine parvovirus among persons with hemophilia receiving Hyate:C porcine factor VIII concentrate

Soucie, J. Michael; Erdman, Dean D.; Evatt, Bruce L.; Anderson, Larry J.; Török, Thomas J.; El-Jamil, Muhydine; Barnhart, Elizabeth R.; Tepper, Maryline; Burrill, H.N.; Pickett, Andy; Mengeling, W. L.

doi:10.1046/j.1537-2995.2000.40060708.x

Cited by 36 publications

(26 citation statements)

References 12 publications

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“…Because the usual dose of Hyate:C for patients with hemophilia involves multiple vials and because many patients receive material from many lots, it is possible that exposure to PERV in recipients was universal [5]. Despite these parenteral exposures, we found no serological evidence of PERV infection in all 88 Hyate:C recipients tested.…”

Section: Discussionmentioning

confidence: 60%

“…These samples included 88 from Hyate:C recipients and 23 from nonrecipients. All 111 patients were identified from among 134 federally funded hemophilia treatment centers (HTCs) in the United States and 4 HTCs in Canada, as described elsewhere [5]. The Hyate:C recipients included persons who had been infused with this product from 1 January 1992 through 15 October 1996.…”

Section: Methodsmentioning

confidence: 99%

“…Current manufacturing practices include rigorous screening of source animals, plasma, and final products to reduce or eliminate contamination with known infectious agents [5]. Screening of source animals, however, cannot eliminate one group of viruses, the porcine endogenous retroviruses (PERVs), because they are expressed from DNA elements present in the genomes of all pigs [6][7][8].…”

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confidence: 99%

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Evidence of Porcine Endogenous Retroviruses in Porcine Factor VIII and Evaluation of Transmission to Recipients with Hemophilia

et al. 2001

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Since 1984, unheated porcine clotting factor VIII (Hyate:C) has been used to treat severe bleeding episodes in persons with hemophilia who have antibodies to human clotting factor. We document the presence of porcine endogenous retrovirus (PERV) in plasma samples of pigs and in clinical lots of Hyate:C. Both gag and pol PERV RNA sequences were detected by reverse-transcriptase (RT) polymerase chain reaction in 13 of 13 lots of Hyate:C tested. Among 10 of these lots, RT activity also was detected, which confirms the presence of retroviral particles. To assess the transmission of PERV to Hyate:C recipients, we tested serum specimens from 88 recipients of Hyate:C and 23 noninfused control subjects for anti-PERV antibodies by using a Western blot assay. None of the samples was positive. Our data document that PERV particles are a common contaminant of Hyate:C products and suggest that the risk of PERV transmission from these percutaneous exposures is very low.

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Section: Discussionmentioning

confidence: 60%

Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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Evidence of Porcine Endogenous Retroviruses in Porcine Factor VIII and Evaluation of Transmission to Recipients with Hemophilia

et al. 2001

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“…One piglet had a slightly increased PPV HI titer from 1:32 at 3 DPI to 1:64 at 21 DPI, which was likely due to testing variation. Serum samples collected from all pigs at 0, 21, and 35 DPI were further tested for PPV DNA with a published PCR assay (51). No PPV viremia was detected from any pigs at DPI 7, 21, or 35, further indicating that the pigs were not infected by PPV.…”

Section: Generation Of Pk-15 Cell Line Free Of Pcv1 Contaminationmentioning

confidence: 99%

Cloned Genomic DNA of Type 2 Porcine Circovirus Is Infectious When Injected Directly into the Liver and Lymph Nodes of Pigs: Characterization of Clinical Disease, Virus Distribution, and Pathologic Lesions

Fenaux

Halbur

Haqshenas

et al. 2002

J Virol

205

201

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Infection of animals with a molecular viral clone is critical to study the genetic determinants of viral replication and virulence in the host. Type 2 porcine circovirus (PCV2) has been incriminated as the cause of postweaning multisystemic wasting syndrome (PMWS), an emerging disease in pigs. We report here for the first time the construction and use of an infectious molecular DNA clone of PCV2 to characterize the disease and pathologic lesions associated with PCV2 infection by direct in vivo transfection of pigs with the molecular clone. The PCV2 molecular clone was generated by ligating two copies of the complete PCV2 genome in tandem into the pBluescript SK (pSK) vector and was shown to be infectious in vitro when transfected into PK-15 cells. Forty specific-pathogen-free pigs at 4 weeks of age were randomly assigned to four groups of 10 each. Group 1 pigs served as uninoculated controls. Pigs in group 2 were each inoculated intranasally with about 1.9 ؋ 10 5 50% tissue culture infective doses of a homogeneous PCV2 live virus stock derived from the molecular clone. Pigs in group 3 were each injected intrahepatically with 200 g of the cloned PCV2 plasmid DNA, and pigs in group 4 were each injected into the superficial iliac lymph nodes with 200 g of the cloned PCV2 plasmid DNA. Animals injected with the cloned PCV2 plasmid DNA developed infection resembling that induced by intranasal inoculation with PCV2 live virus stock. Seroconversion to PCV2-specific antibody was detected in the majority of pigs from the three inoculated groups at 35 days postinoculation (DPI). Viremia, beginning at 14 DPI and lasting 2 to 4 weeks, was detected in the majority of the pigs from all three inoculated groups. There were no remarkable clinical signs of PMWS in control or any of the inoculated pigs. Gross lesions in pigs of the three inoculated groups were similar and were characterized by systemically enlarged, tan lymph nodes and lungs that failed to collapse. Histopathological lesions and PCV2-specific antigen were detected in numerous tissues and organs, including brain, lung, heart, kidney, tonsil, lymph nodes, spleen, ileum, and liver of infected pigs. This study more definitively characterizes the clinical course and pathologic lesions exclusively attributable to PCV2 infection. The data from this study indicate that the cloned PCV2 genomic DNA may replace infectious virus for future PCV2 pathogenesis and immunization studies. The data also suggest that PCV2, although essential for development of PMWS, may require other factors or agents to induce the full spectrum of clinical signs and lesions associated with advanced cases of PMWS.Porcine circovirus (PCV) was originally isolated as a cell culture contaminant of a porcine kidney cell line (PK-15) (56,60). PCV is a small, nonenveloped virus that contains a singlestranded circular DNA genome of about 1.76 kb. PCV is classified in the family of Circoviridae, which consists of three other animal circoviruses (chicken anemia virus [CAV], psittacine beak and feather disease v...

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“…This LOD is within the range used by collaborating laboratories in the establishment of the World Health Organization HEV RNA standard (http://whqlibdoc.who.int/hq/2011/WHO_BS_2011.2175_eng.pdf). In addition, we tested the heparin samples for porcine circovirus 2 (PCV2), an identified adventitious agent of several rotavirus vaccines ( 8 ) and porcine parvovirus (PPV) ( 9 ), a known contaminate of porcine clotting factor hyate:C ( 10 ). Although samples were tested in parallel with PCV2- and PPV- positive spiked controls, we were unable to calculate the LOD for these assays because international standards are not available for these viruses.…”

mentioning

confidence: 99%

Hepatitis E Virus and Porcine-derived Heparin

Crossan¹,

Scobie²,

Godwin

et al. 2013

Emerg. Infect. Dis.

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Investigation of porcine parvovirus among persons with hemophilia receiving Hyate:C porcine factor VIII concentrate

Abstract: The risk of human disease from percutaneous exposure to low levels of PPV seems to be low. Nevertheless, the theoretical risk of human infection with PPV has led to manufacturing changes, including PCR screening of all porcine plasma, which are designed to eliminate this risk.

Cited by 36 publications

References 12 publications

Evidence of Porcine Endogenous Retroviruses in Porcine Factor VIII and Evaluation of Transmission to Recipients with Hemophilia

Evidence of Porcine Endogenous Retroviruses in Porcine Factor VIII and Evaluation of Transmission to Recipients with Hemophilia

Cloned Genomic DNA of Type 2 Porcine Circovirus Is Infectious When Injected Directly into the Liver and Lymph Nodes of Pigs: Characterization of Clinical Disease, Virus Distribution, and Pathologic Lesions

Hepatitis E Virus and Porcine-derived Heparin

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