Investigation of porcine circovirus contamination in human vaccines

Gilliland, Sarah M.; Forrest, Lindsay; Carre, H.; Jenkins, Adrian; Berry, Neil; Martı́n, Javier; Minor, Philip D.; Schepelmann, Silke

doi:10.1016/j.biologicals.2012.02.002

Cited by 39 publications

(32 citation statements)

References 27 publications

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“…[14][15][16][17] The determined range of infectious particles (0-100 per vaccine dose) is compatible with previous reports by two groups which did not detect infective PCV1 in Rotarix™, 14,15 and a third group that was able to successfully infect PK15 and swine testes (ST) cells with a 1:100 dilution of a Rotarix™ dose. 16 Porcine-derived trypsin appears to be the most likely source of the PCV1 DNA detected in Rotarix™.…”

Section: Discussionsupporting

confidence: 78%

“…PCV1 genome sequences were shown to be conserved between the Vero working cell bank, the rotavirus working seed, the intermediate process samples and the final Rotarix™ vaccine. Two specific mutations previously identified in the PCV1 capsid gene 14 were also observed in Rotarix™-related samples when compared with Figure 1. The identification and characterization of PcV1 contamination in the manufacturing process for Rotarix™ and IPV-containing vaccines, respectively.…”

Section: Resultsmentioning

confidence: 85%

“…18 It is unclear why the PCV1 DNA concentration was lower in the poliovirus harvest compared with the rotavirus harvest. It may be related to differences in exposure to contaminated porcine-derived trypsin during the preparation of the respective viral seeds or to differences in the culture process applied during the preparation of the respective cell banks, since PCV1 14 are at position 1163 and 1647, respectively. **sequencing was limited by the amount of recovered material.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Investigation of a regulatory agency enquiry into potential porcine circovirus type 1 contamination of the human rotavirus vaccine,Rotarix™

Dubin

Toussaint

Cassart

et al. 2013

Human Vaccines & Immunotherapeutics

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Section: Discussionsupporting

confidence: 78%

Section: Resultsmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Investigation of a regulatory agency enquiry into potential porcine circovirus type 1 contamination of the human rotavirus vaccine,Rotarix™

Dubin

Toussaint

Cassart

et al. 2013

Human Vaccines & Immunotherapeutics

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“…Antibodies (Ab) in humans share antigenic epitopes with PCV (8). Unexpectedly, PCV1 contamination was recently detected in live poliovirus seeds and commercial live-attenuated human rotavirus vaccines (9,10), and infectious PCV1 was found in the human hepatocellular carcinoma Huh-7 cell line (11). Undoubtedly, PCV exposure poses a potential risk to public health.…”

Section: Importancementioning

confidence: 99%

Circovirus Transport Proceeds via Direct Interaction of the Cytoplasmic Dynein IC1 Subunit with the Viral Capsid Protein

Cao

Lin

Wang

et al. 2015

J Virol

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Microtubule transport of circovirus from the periphery of the cell to the nucleus is essential for viral replication in early infection. How the microtubule is recruited to the viral cargo remains unclear. In this study, we observed that circovirus trafficking is dependent on microtubule polymerization and that incoming circovirus particles colocalize with cytoplasmic dynein and endosomes. However, circovirus binding to dynein was independent of the presence of microtubular ␣-tubulin and translocation of cytoplasmic dynein into the nucleus. The circovirus capsid (Cap) subunit enhanced microtubular acetylation and directly interacted with intermediate chain 1 (IC1) of dynein. N-terminal residues 42 to 100 of the Cap viral protein were required for efficient binding to the dynein IC1 subunit and for retrograde transport. Knockdown of IC1 decreased virus transport and replication. These results demonstrate that Cap is a direct ligand of the cytoplasmic dynein IC1 subunit and an inducer of microtubule ␣-tubulin acetylation. Furthermore, Cap recruits the host dynein/microtubule machinery to facilitate transport toward the nucleus by an endosomal mechanism distinct from that used for physiological dynein cargo. IMPORTANCEIncoming viral particles hijack the intracellular trafficking machinery of the host in order to migrate from the cell surface to the replication sites. Better knowledge of the interaction between viruses and virus proteins and the intracellular trafficking machinery may provide new targets for antiviral therapies. Currently, little is known about the molecular mechanisms of circovirus transport. Here, we report that circovirus particles enter early endosomes and utilize the microtubule-associated molecular motor dynein to travel along microtubules. The circovirus capsid subunit enhances microtubular acetylation, and N-terminal residues 42 to 100 directly interact with the dynein IC1 subunit during retrograde transport. These findings highlight a mechanism whereby circoviruses recruit dynein for transport to the nucleus via the dynein/microtubule machinery. P orcine circovirus (PCV) belongs to the genus Circovirus of the family Circoviridae. This small icosahedral nonenveloped virus is 17 nm in diameter and has circular single-stranded DNA (1). Two genotypes of PCV have been identified: PCV type 1 (PCV1), which is nonpathogenic to pigs (2), and PCV type 2 (PCV2), which is the etiological agent of PCV2-associated disease leading to swine immunosuppression (3-7). Antibodies (Ab) in humans share antigenic epitopes with PCV (8). Unexpectedly, PCV1 contamination was recently detected in live poliovirus seeds and commercial live-attenuated human rotavirus vaccines (9, 10), and infectious PCV1 was found in the human hepatocellular carcinoma Huh-7 cell line (11). Undoubtedly, PCV exposure poses a potential risk to public health.Of the 11 potential open reading frames (ORF) within the PCV genome, four encode viral proteins (12-15). ORF1 encodes a replicase (Rep) that is responsible for the rolling-circl...

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“…12,13 Investigators have documented the presence of full length or nearly full-length sequence of PCV-1 DNA and infectious PCV-1 in Rotarix ® vaccine. 11,[14][15][16][17] In the RotaTeq ® vaccine, short Rotarix® and RotaTeq® vaccines have led to a dramatic reduction in rotavirus disease worldwide. however, the detection of porcine circovirus type 1 (PcV-1) and 2 (PcV-2) DNa in these vaccines raised some safety concerns.…”

Section: Introductionmentioning

confidence: 99%

Detection of PCV-2 DNA in stool samples from infants vaccinated with RotaTeq^®

Esona

Mijatovic-Rustempasic

Yen

et al. 2013

Human Vaccines & Immunotherapeutics

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Rotarix® and RotaTeq® vaccines have led to a dramatic reduction in rotavirus disease worldwide. However, the detection of porcine circovirus type 1 (PCV-1) and 2 (PCV-2) DNA in these vaccines raised some safety concerns. Studies examining shedding of rotavirus in stool from rotavirus vaccine recipients have been performed but no published data exist regarding the shedding of PCV virus in stools of vaccinees. The goal of this study was to determine if PCV-1 and/or PCV-2 is shed in the feces of infants vaccinated with RotaTeq®. Using multiple PCR assays for detection of PCV DNA, we tested for PCV-1 and PCV-2 in 826 stool swab samples collected serially during the first 9 d after vaccination from 102 children vaccinated with RotaTeq®. Since the vaccine is recommended and uptake is high, we did not have samples from unvaccinated infants. A total of 235 (28.5%) samples from 59 vaccine recipients were positive for PCV-2 DNA by one or more assays used in this study. PCV-1 DNA was not detected in RotaTeq® or any of the stool swab extracts. Twenty-two of the 102 vaccine recipients (21.6%) shed RotaTeq® vaccine strain and 10 of these vaccinees (9.8%) were shedding both PCV DNA and rotavirus vaccine RNA. PCV DNA was detected up to 9 d post vaccination and was most frequently detected in the first 5 d after vaccination. This study demonstrated shedding of PCV-2 DNA by RotaTeq® vaccinees but we did not find evidence that this DNA was associated with viable PCV. Findings from this study support the continued use of current rotavirus vaccines.

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Investigation of porcine circovirus contamination in human vaccines

Cited by 39 publications

References 27 publications

Investigation of a regulatory agency enquiry into potential porcine circovirus type 1 contamination of the human rotavirus vaccine,Rotarix™

Investigation of a regulatory agency enquiry into potential porcine circovirus type 1 contamination of the human rotavirus vaccine,Rotarix™

Circovirus Transport Proceeds via Direct Interaction of the Cytoplasmic Dynein IC1 Subunit with the Viral Capsid Protein

Detection of PCV-2 DNA in stool samples from infants vaccinated with RotaTeq^®

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Investigation of porcine circovirus contamination in human vaccines

Cited by 39 publications

References 27 publications

Investigation of a regulatory agency enquiry into potential porcine circovirus type 1 contamination of the human rotavirus vaccine,Rotarix™

Investigation of a regulatory agency enquiry into potential porcine circovirus type 1 contamination of the human rotavirus vaccine,Rotarix™

Circovirus Transport Proceeds via Direct Interaction of the Cytoplasmic Dynein IC1 Subunit with the Viral Capsid Protein

Detection of PCV-2 DNA in stool samples from infants vaccinated with RotaTeq®

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Detection of PCV-2 DNA in stool samples from infants vaccinated with RotaTeq^®