BK Virus: Opportunity Makes a Pathogen

More than 70% of the general population worldwide has serological evidence of exposure to Polyomavirus hominis type 1, better known as BK virus (BKV). BKV infection typically occurs during childhood, without specific symptoms, followed by a state of nonreplicative infection in various tissues, with the urogenital tract as the principal site. Asymptomatic reactivation and low-level replication with viruria is observed in 5% of healthy individuals. Persistent high-level BKV replication is the hallmark of polyomavirus-associated nephropathy in renal transplantation and of hemorrhagic cystitis in bone marrow transplantation. Since these manifestations are rare in other types of immunocompromised patients, the presence of specific cofactors is postulated. The role of BKV in autoimmune disease and cancer is a controversial topic and is difficult to determine, because the pathology no longer depends on BKV replication. This article discusses current views of pathogenesis, diagnosis, and treatmen

Direct identification of differentially expressed genes by cycle sequencing and cycle labelling using the differential display PCR primers

Differential display PCR (DD-PCR) is an mRNA fingerprinting technique to identify differentially expressed genes by comparative display of arbitrarily amplified cDNA subsets. This attractively simple screening method was, however, followed by a labour intensive multistep identification procedure for DD-PCR products. In this report we demonstrate for the mouse mast cell protease 2 (MMCP-2) and the cytotoxic T-lymphocyte associated gene transcript CTLA-1 a streamlined approach by (i) direct cycle sequencing with the upstream differential display (DD) primer, followed by (ii) the PCR based generation of an antisense northern probe with the downstream anchor prime

Rapid Dynamics of Polyomavirus Type BK in Renal Transplant Recipients

BackgroundPolyomavirus type BK-associated nephropathy (PVAN) is an emerging cause of early renal transplant failure. No specific antiviral treatment has been established. Current interventions rely on improving immune functions by reducing immunosuppression. In patients with PVAN, a high BK virus (BKV) load is detectable in plasma. However, the relationship between BKV replication and disease is not well understood MethodsIn a retrospective analysis of BKV plasma load in renal transplant recipients undergoing allograft nephrectomy (n=3) or changes in immunosuppressive regimen (n=12), we calculated viral clearance rates and generation times and estimated the loss of BKV-infected renal cells ResultsAfter nephrectomy, BKV clearance was fast (viral half-life [t 1/2], 1-2 h) or moderately fast (t 1/2, 20-38 h), depending on the sampling density, but it was independent of continued immunosuppressive regimens. After changing immunosuppressive regimens, BKV was cleared with a t 1/2 of 6 h-17 days. Using the basic reproductive ratio, the efficacies of intervention ranged from 7% to 83% (mean, 28%; median, 22%) ConclusionThe results emphasize that high-level BKV replication is a major pathogenetic factor that may have implications for genome rearrangements, immune evasion, and antiviral resistanc

Immune Reconstitution in HIV-Infected Patients

The prognosis of patients infected with human immunodeficiency virus (HIV) type 1 has dramatically improved since the advent of potent antiretroviral therapies (ARTs), which have enabled sustained suppression of HIV replication and recovery of CD4 T cell counts. Knowledge of the function of CD4 T cells in immune reconstitution was derived from large clinical studies demonstrating that primary and secondary prophylaxis against infectious agents, such as Pneumocystis jirovecii (Pneumocystis carinii), Mycobacterium avium complex, cytomegalovirus, and other pathogens, can be discontinued safely once CD4 T cell counts have increased beyond pathogen-specific threshold levels (usually >200 CD4 T cells/mm3) for 3-6 months. The downside of immune reconstitution is an inflammatory syndrome occurring days to months after the start of ART, with outcomes ranging from minimal morbidity to fatal progression. This syndrome can be elicited by infectious and noninfectious antigens. Microbiologically, the possible pathogenic pathways involve recognition of antigens associated with ongoing infection or recognition of persisting antigens associated with past (nonreplicating) infection. Specific antimicrobial therapy, nonsteroidal anti-inflammatory drugs, and/or steroids for managing immune reconstitution syndrome should be considere

Fourth European Conference on Infections in Leukaemia (ECIL-4): Guidelines for Diagnosis and Treatment of Human Respiratory Syncytial Virus, Parainfluenza Virus, Metapneumovirus, Rhinovirus, and Coronavirus

Respiratory viruses have been recognized as a significant cause of morbidity and mortality in patients with leukemia and those undergoing hematopoietic stem cell transplantation. The risk for lower respiratory tract infections and a fatal outcome appears to depend on the intrinsic virulence of the specific community-acquired respiratory virus as well as factors specific to the patient, the underlying disease, and its treatmen