scholarly journals BK Virus-Associated Nephropathy after Renal Transplantation

Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 150
Author(s):  
Yasuhito Funahashi
Keyword(s):  
Renal Transplantation ◽  
Acute Rejection ◽  
Treatment Success ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Immunosuppressive Drugs ◽  
T Antigen ◽  
Bk Virus ◽  
Screening Tests ◽  
Urinary Cytology

Recent advances in immunosuppressive therapy have reduced the incidence of acute rejection and improved renal transplantation outcomes. Meanwhile, nephropathy caused by BK virus has become an important cause of acute or chronic graft dysfunction. The usual progression of infection begins with BK viruria and progresses to BK viremia, leading to BK virus associated nephropathy. To detect early signs of BK virus proliferation before the development of nephropathy, several screening tests are used including urinary cytology and urinary and plasma PCR. A definitive diagnosis of BK virus associated nephropathy can be achieved only histologically, typically by detecting tubulointerstitial inflammation associated with basophilic intranuclear inclusions in tubular and/or Bowman’s epithelial cells, in addition to immunostaining with anti-Simian virus 40 large T-antigen. Several pathological classifications have been proposed to categorize the severity of the disease to allow treatment strategies to be determined and treatment success to be predicted. Since no specific drugs that directly suppress the proliferation of BKV are available, the main therapeutic approach is the reduction of immunosuppressive drugs. The diagnosis of subsequent acute rejection, the definition of remission, the protocol of resuming immunosuppression, and long-term follow-up remain controversial.

Failure to detect papovavirus-associated T antigens in human brain tumor cells by anticomplement immunofluorescence

1980 ◽  
Vol 52 (3) ◽  
pp. 367-370 ◽  
Author(s):  
Hideyuki Kosaka ◽  
Yoshinori Sano ◽  
Yasuhiko Matsukado ◽  
Takeshi Sairenji ◽  
Yorio Hinuma
Keyword(s):  
Brain Tumors ◽  
Human Brain ◽  
Cultured Cells ◽  
Jc Virus ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
T Antigen ◽  
Bk Virus ◽  
Tumor Promoter ◽  
Human Brain Tumor

✓ To probe the possible presence of papovavirus-related T antigen(s) in human brain tumors, the imprinted or cultured cells at various passage levels were examined by anticomplement immunofluorescence using antisera to T antigen of each BK virus, JC virus, and simian virus 40. No T antigen was demonstrated in any tests with cells derived from 69 patients with various brain tumors. Twenty-two tumor cell strains cultured in the presence of a tumor promoter, phorbol ester, also failed to show the T antigen.

scholarly journals Squirrel Monkeys Support Replication of BK Virus More Efficiently than Simian Virus 40: an Animal Model for Human BK Virus Infection

2005 ◽  
Vol 79 (2) ◽  
pp. 1320-1326 ◽  
Author(s):  
Concepcion Zaragoza ◽  
Rui-mei Li ◽  
Gary A. Fahle ◽  
Steven H. Fischer ◽  
Mark Raffeld ◽  
...  
Keyword(s):  
Viral Entry ◽  
Pcr Amplification ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
T Antigen ◽  
Squirrel Monkeys ◽  
Bk Virus ◽  
Saimiri Sciureus ◽  
Viral Copy Number ◽  
Intravenous Inoculation

ABSTRACT We performed experiments to test the suitability of squirrel monkeys (Saimiri sciureus) as an experimental model for BK virus (BKV) and simian virus 40 (SV40) infection. Four squirrel monkeys received intravenous inoculation with BKV Gardner strain, and six squirrel monkeys received intravenous inoculation with SV40 777 strain. Eight of 10 monkeys received immunosuppression therapy, namely, cyclophosphamide subcutaneously either before or both before and after viral inoculation. The presence of viral infection was assessed by quantitative real-time PCR amplification of viral DNA from blood, urine, and 10 tissues. We found that squirrel monkeys were susceptible to infection with BKV, with high viral copy number detected in blood and viral genome detected in all tissues examined. BKV genome was detected in urine from only one monkey, while three monkeys manifested focal interstitial nephritis. BKV T antigen was expressed in renal peritubular capillary endothelial cells. By contrast, SV40 was detected at very low copy numbers in only a few tissues and was not detected in blood. We conclude that the squirrel monkey is a suitable animal for studies of experimental BKV infection and may facilitate studies of viral entry, pathogenesis, and therapy.

scholarly journals Tubulointerstitial Nephritis Due to a Mutant Polyomavirus BK Virus Strain, BKV(Cin), Causing End-Stage Renal Disease

1998 ◽  
Vol 36 (6) ◽  
pp. 1660-1665 ◽  
Author(s):  
R. D. Smith ◽  
J. H. Galla ◽  
K. Skahan ◽  
P. Anderson ◽  
C. C. Linnemann ◽  
...  
Keyword(s):  
Tubulointerstitial Nephritis ◽  
Pcr Amplification ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Buffy Coat ◽  
T Antigen ◽  
Bk Virus ◽  
Coding Region ◽  
Viral Dna ◽  
Cycle Sequencing

A renal biopsy from a 36-year-old man with AIDS showed a severe tubulointerstitial nephritis with intranuclear inclusions in epithelial cells. Electron microscopy revealed the characteristic findings of a polyomavirus (PyV) infection, and immunofluorescence indicated the presence of BK virus (BKV) antigen. Inoculation of rhesus monkey kidney cell cultures both with urine and with buffy coat blood cells resulted in a cytopathic response which was subsequently confirmed to be due to BKV. Further characterization of the viral DNA from the kidney by PCR amplification and Southern blot analysis with PyV and strain-specific primers and probes indicated that the virus was closely related to the BK(Dun) strain but different in its apparent sequence arrangement. Subsequent cycle sequencing showed a dinucleotide mutation of TG→AA which substitutes hydrophilic Gln for hydrophobic Leu in a sequence homologous to an origin DNA-binding domain of simian virus 40 T antigen. It is suggested that the mutation and a coding region rearrangement of this strain of BKV designated BKV(Cin) has the potential to alter viral DNA replication and enhance pathogenicity.

scholarly journals Novel Mechanisms of E2F Induction by BK Virus Large-T Antigen: Requirement of Both the pRb-Binding and the J Domains

1998 ◽  
Vol 18 (3) ◽  
pp. 1746-1756 ◽  
Author(s):  
Kimya F. Harris ◽  
Joan B. Christensen ◽  
Eric H. Radany ◽  
Michael J. Imperiale
Keyword(s):  
Cellular Proliferation ◽  
Protein Complexes ◽  
Family Members ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
T Antigen ◽  
Bk Virus ◽  
Large T Antigen ◽  
Cellular Mechanisms ◽  
Sv40 Large T Antigen

ABSTRACT E2F activity is regulated in part by the retinoblastoma family of tumor suppressor proteins. Viral oncoproteins, such as simian virus 40 (SV40) large-T antigen (TAg), adenovirus E1A, and human papillomavirus E7, can disrupt the regulation of cellular proliferation by binding to pRb family members and dissociating E2F-pRb family protein complexes. BK virus (BKV), which infects a large percentage of the human population and has been associated with a variety of human tumors, encodes a TAg homologous to SV40 TAg. It has been shown that BKV TAg, when expressed at low levels, does not detectably bind to pRb family members, yet it induces a serum-independent phenotype and causes a decrease in the overall levels of pRb family proteins. The experiments presented in this report show that, despite the lack of TAg-pRb interactions, BKV TAg can induce transcriptionally active E2F and that this induction does in fact require an intact pRb-binding domain as well as an intact J domain. In addition, E2F-pRb family member complexes can be detected in both BKV and SV40 TAg-expressing cells. These results suggest the presence of alternate cellular mechanisms for the release of E2F in addition to the well-established model for TAg-pRb interactions. These results also emphasize a role for BKV TAg in the deregulation of cellular proliferation, which may ultimately contribute to neoplasia.

scholarly journals A truncated T antigen expressed from an alternatively spliced BK virus early mRNA

2009 ◽  
Vol 90 (5) ◽  
pp. 1238-1245 ◽  
Author(s):  
Johanna R. Abend ◽  
Amy E. Joseph ◽  
Dweepanita Das ◽  
Deniz B. Campbell-Cecen ◽  
Michael J. Imperiale
Keyword(s):  
Jc Virus ◽  
Stop Codon ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
T Antigen ◽  
Bk Virus ◽  
T Antigens ◽  
Reading Frame ◽  
Early Region ◽  
Alternatively Spliced

The early region of BK virus (BKV) is known to encode two well-characterized tumour (T) antigens, large T antigen (TAg) and small T antigen (tAg). In this study, we provide evidence of a third early BKV mRNA that codes for an additional early region product with an apparent molecular mass of 17–20 kDa. This truncated form of TAg (truncTAg) is expressed from an alternatively spliced mRNA that is derived from the excision of a second intron from the mRNA encoding TAg. The first 133 aa of truncTAg are identical to those of TAg but the additional splice results in translation from a different reading frame, adding three new amino acids before reaching a stop codon. TruncTAg is expressed in both BKV-transformed and lytically infected cells and it is found to be primarily localized to the nucleus. The function of BKV truncTAg is likely to be relevant to transformation, similar to the additional T antigens of simian virus 40, JC virus and mouse polyomavirus.

Structure and synthesis of a simian virus 40 super T-antigen.

1982 ◽  
Vol 44 (3) ◽  
pp. 963-973 ◽  
Author(s):  
M Lovett ◽  
C E Clayton ◽  
D Murphy ◽  
P W Rigby ◽  
A E Smith ◽  
...  
Keyword(s):  
Simian Virus 40 ◽  
Simian Virus ◽  
T Antigen
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