Peripheral blood mononuclear cells represent a reservoir of bovine papillomavirus DNA in sarcoid-affected equines

Brandt, Sabine; Haralambus, Rhea; Schoster, Angelika; Kirnbauer, Reinhard; Stanek, C

doi:10.1099/vir.0.83568-0

Cited by 84 publications

(101 citation statements)

References 41 publications

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“…In veterinary medicine, previous studies have shown both the expression of E5 oncogene and the presence of E5 oncoprotein of BPV-2 in PBMCs (Brandt et al, 2008;Roperto et al, 2008). In human medicine, neither viral oncoproteins nor HPV-specific RNA are known to occur in PBMCs of PV-infected cancer patients (Pao et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

PBMCs are additional sites of productive infection of bovine papillomavirus type 2

Roperto

Comazzi

Ciusani

et al. 2011

Journal of General Virology

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Bovine papillomavirus type 2 (BPV-2) is an oncogenic virus infecting both epithelial and mesenchymal cells. Its life cycle, similar to other papillomaviruses (PVs), appears to be linked to epithelial differentiation. Human and bovine PVs have been known to reside in a latent, episomal form in PBMCs; therefore, it is believed that blood cells, like all mesenchymal cells, function as non-permissive carriers. Here, for the first time in veterinary and comparative medicine, the BPV-2 E5 oncoprotein and the major structural L1 capsid protein, known to be expressed only in productive infections, were shown to occur in defined subsets of PBMCs. E5 oncoprotein was detected in sorted T-and B-cells as well as in monocytes by flow cytometry and Western blot analysis. However, CD4 + and CD8 + lymphocytes appeared to be the main circulating targets of the virus, thus possibly representing the most important reservoir of active BPV-2 in blood. L1 protein was identified by flow cytometry in a population of blood cells recognized as lymphocytes by morphological scatter properties. Western blot analysis was performed on lysates obtained from the sorted subpopulations of PBMCs and detected L1 protein in CD4 + and CD8 + cells only. Thus, this study showed that CD4 + and CD8 + lymphocytes are permissive for BPV-2 and are new, hitherto unknown sites of productive PV infection. In light of these observations, the life cycle of PVs needs to be revisited to gain novel insights into the epidemiology of BPV infection and the pathogenesis of related diseases. INTRODUCTIONBovine papillomaviruses (BPVs) are a heterogeneous group of viruses responsible for tumours of the skin, genital and paragenital area, eye, upper gastrointestinal tract and urinary bladder (IARC, 2007). BPVs, like all other papillomaviruses (PVs), are usually strictly species specific. However, cases of cross-species infection are known to occur. BPV type 1 (BPV-1) and BPV-2, belonging to the genus Deltapapillomavirus (de Villiers et al., 2004), are responsible for infections in equids resulting in sarcoids (Chambers et al., 2003;Trenfield et al., 1985), as well as in bison and water buffaloes leading to warts (Literák et al., 2006;Silvestre et al., 2009). In addition, a variant of BPV-8, classified in the genus Epsilonpapillomavirus, also causes papillomas of the skin in bison (Tomita et al., 2007). More recently, it has been suggested that BPVs could be responsible for cutaneous sarcoids in cats and captive African lions (Munday & Knight, 2010;Orbell et al., 2010).BPV-1 and -2 are closely related serotypes (Shafti-Keramat et al., 2009) and can infect both epithelial and mesenchymal cells. Similar to other PVs, BPV-1/-2 replication and virion production are confined to the epithelial region of the lesions, whilst infection of mesenchymal cells appears to be non-productive (Campo, 2006;Shafti-Keramat et al., 2009).BPV-2 is known to play a central role in bladder carcinogenesis of adult cattle reared on pasturelands rich in bracken fern. In these animals, tumours of the u...

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Section: Discussionmentioning

confidence: 99%

PBMCs are additional sites of productive infection of bovine papillomavirus type 2

Roperto

Comazzi

Ciusani

et al. 2011

Journal of General Virology

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“…In cattle feeding on bracken fern, BPV-4 is associated with upper alimentary tract cancer. BPV-1 and BPV-2 are associated with both fibropapillomas in cattle and sarcoids in equids (Brandt et al, 2008;Nasir and Campo, 2008). BPV-2 infection in the presence of environmental carcinogens, such as ptaquiloside, a toxic principle of bracken fern (Pteridium aquilinum), has been associated with urinary bladder neoplasic lesions in adult cattle, in which chronic enzootic hematuria is the most important clinical sign (Hopkins, 1986;Campo et al, 1992;Campo, 1997).…”

Section: Introductionmentioning

confidence: 99%

Simultaneous presence of bovine papillomavirus in blood and in short-term lymphocyte cultures from dairy cattle in Pernambuco, Brazil

Diniz

Melo²,

Santos³

et al. 2009

Genet. Mol. Res.

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ABSTRACT. Bovine papillomaviruses (BPV) are the causal agents of benign and malignant lesions; they can cause dramatic economic losses in cattle. Although 10 virus types have been described, three types are most common in tumors, namely BPV-1, -2 and -4. Previous studies have reported BPV in blood cells and the possibility of blood acting as a latent virus site and/or transmission agent of virus dissemination. We studied a Holstein dairy herd in Pernambuco, Brazil, in which several animals showed severe cutaneous papillomatosis, without previous determination of BPV types. Blood samples and short-term lymphocyte cultures were collected from 54 cows. We compared the BPV types detected in peripheral blood to those identified in the respective lymphocyte cultures: BPV-1 was detected in 74% and BPV-2 in 87% of the whole blood samples. Simultaneous virus presence (BPV-1 and BPV-2) was found in 65% of the blood samples. BPV-1 or BPV-2 were detected in the lymphocyte cultures in 93% of the samples, and both in 89%. The detection of viral DNA in whole blood and in lymphocyte cultures is evidence that this virus is carried by lymphocytes.

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“…Comparing levels of average heterozygosity, mean number of alleles per loci, effective number of alleles, mean range of microsatellite repeats and microsatellite variance estimates between a population of interest and its free-ranging counterpart are useful to determine loss of genetic variation. The appearance of sarcoid tumours in equids has been correlated with specific genetic haplotypes (Chambers et al 2003) with the involvement of BPV in the formation of sarcoid tumour in equids proven (Lohr et al 2005;Brandt et al 2008) and correlated with down-regulation of immune system genes (Ashrafi et al 2006;Yuan et al 2008). The only previous epizootic of sarcoid tumour reported was in horses, with four of the five affected individuals being members of a highly inbred herd (Ragland et al 1966).…”

Section: Discussionmentioning

confidence: 99%

Comparative Genetics of Sarcoid Tumour-Affected and Non-Affected Mountain Zebra (Equus zebra) Populations

Sasidharan

Ludwig

Harper

et al. 2011

South African Journal of Wildlife Research

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Peripheral blood mononuclear cells represent a reservoir of bovine papillomavirus DNA in sarcoid-affected equines

Cited by 84 publications

References 41 publications

PBMCs are additional sites of productive infection of bovine papillomavirus type 2

PBMCs are additional sites of productive infection of bovine papillomavirus type 2

Simultaneous presence of bovine papillomavirus in blood and in short-term lymphocyte cultures from dairy cattle in Pernambuco, Brazil

Comparative Genetics of Sarcoid Tumour-Affected and Non-Affected Mountain Zebra (Equus zebra) Populations

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