BK polyomavirus serotype-specific antibody responses in blood donors and kidney transplant recipients with and without new-onset BK polyomavirus-DNAemia: A Swiss Transplant Cohort Study.

BK polyomavirus (BKPyV) causes premature renal failure in 10% to 30% of kidney transplant recipients (KTRs). Current guidelines recommend screening for new-onset BKPyV-DNAemia/nephropathy and reducing immunosuppression to regain BKPyV-specific immune control. Because BKPyV encompasses 4 major genotype (gt)-encoded serotypes (st1,-2,-3,-4), st-specific antibodies may inform the risk and course of BKPyV-DNAemia/nephropathy.

BK Polyomavirus-Specific CD8 T-Cell Expansion In Vitro Using 27mer Peptide Antigens for Developing Adoptive T-Cell Transfer and Vaccination.

Background: BK polyomavirus (BKPyV) remains a significant cause of premature kidney transplant failure. In the absence of effective antivirals, current treatments rely on reducing immunosuppression to regain immune control over BKPyV replication. Increasing BKPyV-specific CD8 T cells correlate with clearance of BKPyV DNAemia in kidney transplant patients.

BK Polyomavirus Evades Innate Immune Sensing by Disrupting the Mitochondrial Network and Promotes Mitophagy.

Immune escape contributes to viral persistence, yet little is known about human polyomaviruses. BK-polyomavirus (BKPyV) asymptomatically infects 90% of humans but causes premature allograft failure in kidney transplant patients. Despite virus-specific T cells and neutralizing antibodies, BKPyV persists in kidneys and evades immune control as evidenced by urinary shedding in immunocompetent individuals.

JC polyomavirus-specific antibody responses in pediatric kidney transplant recipients.

BKPyV is widely recognized in KTRs, but little is known about rates of primary and secondary JCPyV exposure in pediatric KTRs. We evaluated JCPyV exposure in pediatric KTRs using antibody responses in the first 12 months post-transplant. Of 46 children transplanted between 2009 and 2014, 6 lacked any samples for serologic testing, leaving 40 KTRs for study.

BK polyomavirus viremia and antibody responses of pediatric kidney transplant recipients in Finland.

Background: BKPyV is an important cause of premature graft failure after KT. Most clinical studies describe BKPyV infection in adult KT patients. We studied the prevalence of post-transplant BKPyV viremia, serology, and graft function in pediatric KT recipients.

High-level JCPyV viruria after kidney transplantation-Clinical and histopathological findings.

Background: The significance of JC polyomavirus (JCPyV) after kidney transplantation ranges from irrelevant to full-blown nephropathy or PML.

Objectives: To investigate the clinical significance of high-level JCPyV viruria and JCPyV primary infections after kidney transplantation.

Study Design: JCPyV viruria was detected in routine screening by quantitative real-time PCR in 40/238 kidney transplant recipients and was high-level (>10 copies/ml) in 17 patients.

Simultaneous BK Polyomavirus (BKPyV)-associated nephropathy and hemorrhagic cystitis after living donor kidney transplantation.

BK polyomavirus (BKPyV) commonly reactivates after kidney transplantation, and can cause polyomavirus-associated nephropathy (PyVAN), whereas after allogeneic stem cell transplantation the most frequent manifestation of BKPyV is polyomavirus-associated hemorrhagic cystitis (PyVHC). Despite high-level BKPyV replication in both, the pathogenesis and manifestation of both BKPyV entities appears to differ substantially. We describe an unusual case of simultaneous PyVAN and PyVHC presenting with acute symptoms in a BKPyV-IgG positive recipient eight months after kidney transplantation from a haploidentical living donor, who was BKPyV-IgG negative.

Comparing effects of BK virus agnoprotein and herpes simplex-1 ICP47 on MHC-I and MHC-II expression.

Background: Among human polyomaviruses, only BK virus (BKV) and JC virus (JCV) encode an agnoprotein upstream of VP1 on the viral late transcript. BKV agnoprotein is abundantly expressed late in the viral life cycle, but specific cellular and humoral immune responses are low or absent. We hypothesized that agnoprotein might contribute to BKV immune evasion by downregulating HLA expression, similar to Herpes simplex virus-1 ICP47.

CMX001 (1-O-hexadecyloxypropyl-cidofovir) inhibits polyomavirus JC replication in human brain progenitor-derived astrocytes.

Polyomavirus JC (JCV) replication causes progressive multifocal leukoencephalopathy (PML), a frequently fatal brain disease in immunodeficient patients, yet antiviral drugs are lacking. We characterized the lipid conjugate 1-O-hexadecyloxypropyl-cidofovir (CMX001) regarding JCV (Mad-4) replication in human brain progenitor-derived astrocytes (PDA) and the simian virus 40 (SV40) large-T-antigen-expressing COS-7 cells up to 7 days postinfection (dpi). We examined JCV loads by PCR, the infection rate by immunofluorescence, and host cell toxicity by WST-1 and BrdU incorporation assays.

Influence of antiretroviral therapy on programmed death-1 (CD279) expression on T cells in lymph nodes of human immunodeficiency virus-infected individuals.

Human immunodeficiency virus infection leads to T-cell exhaustion and involution of lymphoid tissue. Recently, the programmed death-1 pathway was found to be crucial for virus-specific T-cell exhaustion during human immunodeficiency virus infection. Programmed death-1 expression was elevated on human immunodeficiency virus-specific peripheral blood CD8+ and CD4+ T cells and correlated with disease severity.

Suppression of short interfering RNA-mediated gene silencing by the structural proteins of hepatitis C virus.

Viruses have evolved strategies to overcome the antiviral effects of the host at different levels. Besides specific defence mechanisms, the host responds to viral infection via the interferon pathway and also by RNA interference (RNAi). However, several viruses have been identified that suppress RNAi.

Apoptosis and pathogenesis of melanoma and nonmelanoma skin cancer.

Skin cancers, i.e., basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and melanoma, belong to the most frequent tumors.

Gene silencing of transcription factor Gli2 inhibits basal cell carcinomalike tumor growth in vivo.

Basal cell carcinoma (BCC) belongs worldwide to the most frequent malignancy among Caucasians. The understanding of the molecular mechanisms of BCC formation, which is a prerequisite for the development of efficient new therapies, is still incomplete. The formation of sporadic BCCs in the skin is associated with uncontrolled hedgehog signaling, and the transcription factor Gli2 has been identified as a key mediator or effector of this signaling.

Role of apoptosis in basal cell and squamous cell carcinoma formation.

Long-term ultraviolet-light (UV) exposure of human skin epidermis is associated with an increased risk for the development of skin cancers, such as melanoma, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). UV radiation not only induces DNA damage in epidermal cells, it also interferes with skin homeostasis, which is maintained by a unique distribution pattern of apoptosis-inducing and -preventing molecules. If the DNA damage is not repaired or the damaged cells are not eliminated by apoptosis, the consequence can be cell transformation, uncontrolled proliferation and eventually skin tumor formation.

Enhanced gene silencing by the application of multiple specific small interfering RNAs.

Small interfering RNA duplexes (siRNA) induce gene silencing in various eukaryotic cells, although usually in an incomplete manner. Using chemically synthesized siRNAs targeting the HIV-1 co-receptor CXCR4 or the apoptosis-inducing Fas-ligand (FasL), co-transfection of cells with two or more siRNA duplexes targeting different sites on the same mRNA resulted in an enhanced gene silencing compared with each single siRNA. This was shown in the down-regulation of protein and mRNA expression, and functionally in the inhibition of CXCR4-mediated HIV infection and of FasL-mediated cell apoptosis.

Fas ligand downregulation with antisense oligonucleotides in cells and in cultured tissues of normal skin epidermis and basal cell carcinoma.

Fas ligand (FasL), a member of the tumor necrosis factor family, induces apoptosis upon interaction with Fas-receptor-expressing cells. FasL normally plays an important immune regulatory role, but it can also cause severe skin diseases if overexpressed and it may serve some tumors for immune evasion. Thus, in situ inhibition of FasL expression with antisense oligonucleotides in patients may be a novel approach to overcome its pathogenic role.

Tumor necrosis factor-related, apoptosis-inducing ligand supports growth of mouse mastocytoma tumors by killing tumor-infiltrating macrophages.

TRAIL antisense transfected mastocytoma cells (R56VTas) injected into syngeneic DBA/2 mice demonstrate significantly delayed tumor growth compared to mock transfected cells (R56VTMo). TRAIL expression in R56VTas cells was successfully, albeit not completely, downregulated, as shown by Western blots, flow-cytometric analysis and functionally by loss of cytolytic activity against TRAIL-R-bearing target cells. Immunohistochemic and immunoblotting analyses of ex vivo tumors confirmed the lower expression of TRAIL by the antisense transfection compared to the mock transfection.

Intralesional interferon in basal cell carcinoma: how does it work?

Basal cell carcinoma (BCC) is the most common skin cancer among Caucasians, and its incidence is increasing. Intralesional injection of interferon alpha (IFN alpha) has been shown to provide a safe and effective treatment for BCCs. The predominant mechanism for the effect of IFN alpha on BCC has been partially identified.

Differential expression of viral Bcl-2 encoded by Kaposi's sarcoma-associated herpesvirus and human Bcl-2 in primary effusion lymphoma cells and Kaposi's sarcoma lesions.

Expression of human herpesvirus 8 viral Bcl-2 protein was demonstrated in spindle cells of late-stage Kaposi's sarcoma lesions but not in primary effusion lymphoma cell lines. In contrast, strong expression of human Bcl-2 was found in stimulated primary effusion lymphoma cells, whereas in Kaposi's sarcoma lesions preferential mononuclear cells, and to a lesser extent spindle cells, stained positive.