Anti-HIV effects of chloroquine: inhibition of viral particle glycosylation and synergism with protease inhibitors

OBJECTIVE: We tested the effects of chloroquine (CQ) on glycosylation of HIV particles and in combination with protease inhibitors (PIs) on HIV replication and on P-glycoprotein (P-gp)/multidrug resistance protein-1 (MRP1). DESIGN: CD4 cell lines were infected with laboratory strains and peripheral blood mononuclear cells were infected with primary isolates for evaluation of the anti-HIV effects. Peripheral blood lymphocytes were evaluated for of P-gp and MRP1 functions. METHODS: HIV replication was assessed by enzyme-linked immunosorbent assay. HIV glycosylation was measured by metabolic labeling of viral particles with [H] glucosamine. Synergism was tested using isobolograms. P-gp and MRP1 functions were assayed using rhodamine 123 (Rh123) and carboxyfluorescein (CF) efflux assays, respectively. RESULTS: CQ alone inhibited HIV replication and glycosylation in a dose-dependent manner. In combination with indinavir (IDV), ritonavir, or saquinavir (SQV), CQ had a synergistic effect at concentrations found in plasma of subjects receiving malaria prophylaxis. CQ decreased the 50% effective concentration of IDV in primary isolates from Africa and restored the response to IDV or SQV in 3 PI-resistant isolates. CQ increased the block of Rh123 and CF efflux activity exerted by PIs. CONCLUSION: The inhibitory effects of CQ on HIV glycosylation are associated with synergistic effects in combination with PIs. The CQ/PI combination exerts combined inhibitory effects on P-gp and MRP1 function.     

Monitoring of KI and WU polyomaviruses in hematopoietic stem cell transplant patients

Primary infection with KIPyV and WUPyV polyomaviruses occurs early in childhood followed by lifelong persistence in the body. Polyomavirus reactivation can occur in the presence of impaired immunity as in hematological malignancies or during immunosuppresssion induced by medications. In this study, reactivation of KIPyV and WUPyV was monitored by conventional PCR in plasma samples of 26 stem cell transplant patients and in 26 related bone marrow donors. Plasma samples from transplant patients were collected immediately after the end of conditioning regimen and up to 270 days after transplant. All plasma samples from transplant patients were negative for KIPyV and WUPyV DNA. Instead, KIPyV DNA was detected in two bone marrow donors. There was no evidence of KIPyV transmission from the donor to the recipient. The data suggest that detection of KIPyV in plasma is sporadic and that KPIyV and WUPyV do not affect the post‐transplant clinical course. However, further studies on a larger sample size and more sensitive PCR methods are needed to confirm these observations. J. Med. Virol. 85: 1122–1124, 2013. © 2013 Wiley Periodicals, Inc.     

The human polyomaviruses KI and WU: virological background and clinical implications

In 2007, two novel polyomaviruses KI and WU were uncovered in the respiratory secretions of children with acute respiratory symptoms. Seroepidemiological studies showed that infection by these viruses is widespread in the human population. Following these findings, different biological specimens and body compartments have been screened by real‐time PCR in the attempt to establish a pathogenetic role for KI polyomavirus (KIPyV) and WU polyomavirus (WUPyV) in human diseases. Although both viruses have been found mainly in respiratory tract samples of immunocompromised patients, a clear causative link with the respiratory disease has not been established. Indeed, the lack of specific clinical or radiological findings, the frequent co‐detection with other respiratory pathogens, the detection in subjects without signs or symptoms of respiratory disease, and the variability of the viral loads measured did not allow drawing a definitive conclusion. Prospective studies carried out on a large sample size including both immunocompromised and immunocompetent patients with and without respiratory symptoms are needed. Standardized quantitative real‐time PCR methods, definition of a clear clinical cutoff value, timing in the collection of respiratory samples, are also crucial to understand the pathogenic role, if any, of KIPyV and WUPyV in human pathology.