Shedding of polyomavirus in the saliva of immunocompetent individuals

Robaina, Tatiana Ferreira; Mendes, Gabriella S.; Benati, Fabrício José; Pena, Giselle A.; Silva, Raquel C.; Montes, Miguel A.R.; Janini, Maria Elisa Rangel; Câmara, Fernando Portela; Santos, Norma

doi:10.1002/jmv.23453

Cited by 23 publications

(24 citation statements)

References 29 publications

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“…Based on our observation that BKPyV can also infect salivary gland cells in vitro and is associated with pathology in vivo in humans (28, 29, 45, 46), three drugs with demonstrated anti BKPyV activity in kidney cells, CPRO, CDV and LEF were assessed for BKPyV inhibition in salivary gland cells in vitro. It is clear that the kinetics of salivary gland infection are delayed compared to BKPyV infection in kidney cells (Figure 1), thus the response to the agents may vary based on time post infection.…”

Section: Discussionmentioning

confidence: 99%

Effect of Leflunomide, Cidofovir and Ciprofloxacin on replication of BKPyV in a salivary gland in vitro culture system

2015

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BK polyomavirus (BKPyV) is a known kidney tropic virus that has been detected at high levels in HIV-associated salivary gland disease (HIV-SGD), one of the most important AIDS associated oral lesions. BKPyV has been detected in HIV-SGD patient saliva and replicates in salivary gland cells in vitro. BKPyV antivirals are currently in wide use to guard against BKPyV mediated organ rejection in kidney transplant recipients. The goal of this study was to investigate the inhibitory effects of three such antiviral agents, ciprofloxacin, cidofovir, and leflunomide in BKPyV infected salivary gland cells. Human salivary gland cells, and Vero cells, were infected with BKPyV, treated with antiviral drugs and assessed for BKPyV gene expression and viral replication for up to 5 days post infection. The kinetics of BKPyV replication were different in salivary gland cells compared to kidney cells. Ciprofloxacin and cidofovir had minimal effect on metabolic activity and host cell DNA replication, however, cell toxicity was detected at the protein level with leflunomide treatment. Ciprofloxacin decreased BKV T Ag and VP1 mRNA expression by at least 50% in both cell types, and decreased T Ag protein expression at days 3 and 4 post infection. A 2.5 – 4 log decrease in intracellular DNA replication and a 2 – 3 log decrease in progeny release were detected with ciprofloxacin treatment. Cidofovir and leflunomide also inhibited BKPyV gene expression and DNA replication. The three drugs diminished progeny release by 30–90% and 2 – 6 fold decreases in infectious virus were detected post drug treatment by fluorescence focus assay. Additionally, three clinical BKPyV isolates were assessed for their responses to these agents in vitro. Cidofovir and leflunomide, but not ciprofloxacin treatment resulted in statistically significant inhibition of BKPyV progeny release from salivary gland cells infected with HIV-SGD BKPyV isolates. All three drugs decreased progeny release from cells infected with a transplant derived viral isolate. In conclusion, treatment of human salivary gland cells with each of the three drugs produced modest decreases in BKPyV genome replication. These data highlight the need for continued studies to discover more effective and less toxic drugs that inhibit BKPyV replication in salivary gland cells.

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Section: Discussionmentioning

confidence: 99%

Effect of Leflunomide, Cidofovir and Ciprofloxacin on replication of BKPyV in a salivary gland in vitro culture system

2015

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“…Robaina et al (13) demonstrated that the reactivation of primary infection with polyomaviruses also applies to immunocompetent persons. In saliva samples collected from people aged 15-75 years, about 23.4% were positive for at least one polyomavirus, including 12.7% WU and 2.4% KI.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of Polyomaviruses in Polish patients

Badura

Dworzański

Polz

et al. 2014

Current Issues in Pharmacy and Medical Sciences

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The aim of our study was to investigate the prevalence of new polyomaviruses KIPyV and WUPyV in the Polish population in the Lublin region. In it, we demonstrated that the prevalence of this viruses is low - 1.1% WU and 3.4% KI. The viruses are most commonly detected in materials from the respiratory tract, both in children and the elderly. Polyomaviruses KI and WU in co-infection, often occur with other respiratory viruses (influenza, enterovirus).

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“…BKV is generally accepted to latently reside in epithelial cells lining the urogenital tract. However, in immunocompetent individuals, the virus has also been detected in the central nervous system, stool samples, and saliva (19)(20)(21). Since BKV-specific T cells are present in the circulation, one could theorize that they are trafficking to a site of (re)activation.…”

Section: Fig 3 Bkv-specific Cd8mentioning

confidence: 99%

Phenotypic and Functional Characterization of Circulating Polyomavirus BK VP1-Specific CD8 ⁺ T Cells in Healthy Adults

Aalderen

Remmerswaal

Heutinck

et al. 2013

J Virol

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The human polyomavirus BK virus (BKV) establishes a latent and asymptomatic infection in the majority of the population. In immunocompromised individuals, the virus frequently (re)activates and may cause severe disease such as interstitial nephritis and hemorrhagic cystitis. Currently, the therapeutic options are limited to reconstitution of the antiviral immune response. T cells are particularly important for controlling this virus, and T cell therapies may provide a highly specific and effective mode of treatment. However, little is known about the phenotype and function of BKV-specific T cells in healthy individuals. Using tetrameric BKV peptide-HLA-A02 complexes, we determined the presence, phenotype, and functional characteristics of circulating BKV VP1-specific CD8 ؉ T cells in 5 healthy individuals. We show that these cells are present in low frequencies in the circulation and that they have a resting CD45RA ؊ CD27 ؉ memory and predominantly CCR7 ؊ CD127 ؉ KLRG1 ؉ CD49d hi CXCR3 hi T-bet int Eomesodermin lo phenotype. Furthermore, their direct cytotoxic capacity seems to be limited, since they do not readily express granzyme B and express only little granzyme K. We compared these cells to circulating CD8 ؉ T cells specific for cytomegalovirus (CMV), Epstein-Barr virus (EBV), and influenza virus (Flu) in the same donors and show that BKV-specific T cells have a phenotype that is distinct from that of CMV-and EBV-specific T cells. Lastly, we show that BKV-specific T cells are polyfunctional since they are able to rapidly express interleukin-2 (IL-2), gamma interferon (IFN-␥), tumor necrosis factor ␣, and also, to a much lower extent, MIP-1␤ and CD107a. In healthy individuals, the polyomavirus BK virus (BKV) establishes a latent, or "smoldering," but asymptomatic infection. However, in immunocompromised individuals, the virus frequently escapes the normal immunological surveillance to become systemically active, after which it may cause severe pathology. BKV elicits interstitial nephritis of the allograft in about 5% of kidney transplant recipients, making it an important cause of graft failure and graft loss. In up to 30% of hematopoietic stem cell transplant (HSCT) recipients, the virus induces hemorrhagic cystitis, thereby significantly contributing to morbidity and length of hospitalization (1).Currently, the main mode of therapy for patients suffering from BKV infection comprises reconstitution of the immunological antiviral response. In solid organ transplant recipients, this is achieved through tapering of the immunosuppressive medication. Unfortunately, this comes at the cost of increased allograft rejection, and in HSCT recipients this is an unattractive approach due to a considerable increase in the risk of graft-versus-host disease. So far, antiviral agents, such as cidofovir and leflunomide, have shown little effect on BKV replication in vivo (1). It is therefore crucial to develop new modes of therapy. In this regard, the normal T cell response was shown to be very important for keeping BKV at b...

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Shedding of polyomavirus in the saliva of immunocompetent individuals

Cited by 23 publications

References 29 publications

Effect of Leflunomide, Cidofovir and Ciprofloxacin on replication of BKPyV in a salivary gland in vitro culture system

Effect of Leflunomide, Cidofovir and Ciprofloxacin on replication of BKPyV in a salivary gland in vitro culture system

Prevalence of Polyomaviruses in Polish patients

Phenotypic and Functional Characterization of Circulating Polyomavirus BK VP1-Specific CD8 ⁺ T Cells in Healthy Adults

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Shedding of polyomavirus in the saliva of immunocompetent individuals

Cited by 23 publications

References 29 publications

Effect of Leflunomide, Cidofovir and Ciprofloxacin on replication of BKPyV in a salivary gland in vitro culture system

Effect of Leflunomide, Cidofovir and Ciprofloxacin on replication of BKPyV in a salivary gland in vitro culture system

Prevalence of Polyomaviruses in Polish patients

Phenotypic and Functional Characterization of Circulating Polyomavirus BK VP1-Specific CD8 + T Cells in Healthy Adults

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Phenotypic and Functional Characterization of Circulating Polyomavirus BK VP1-Specific CD8 ⁺ T Cells in Healthy Adults