Guy Boivin

..Thus, active viral replication as determined by a high CMV DNA load in PBL is reflected by expression of the late CMV transcript in the same cells and by the presence of CMV DNA in plasma...

..5 and 98.9% compared to 81.6 and 94.7% for the antigenic test. In conclusion, our multiplex real-time PCR assay combines both rapidity and sensitivity for detecting the most important respiratory viral pathogens in children...

..In conclusion, amino acid changes at residue I223 may alter the NAI susceptibilities of pH1N1 variants without compromising fitness. Consequently, I223R and I223V mutations, alone or with H275Y, need to be thoroughly monitored...

..However, risk factors for severe hMPV disease remain unknown. We comparatively assessed environmental, host, and viral determinants for severe hMPV and RSV infections...

..A good correlation was generally found between replication kinetics of DNA pol mutants and their neurovirulence potential in mice whereas such correlation was not straightforward for TK mutants...

..Drug-resistant cytomegalovirus (CMV) infections can cause significant morbidity among high-risk transplant recipients...

..Both prophylactic and, to a lesser extent, therapeutic administration of MAb 338 improved acute and late consequences of HMPV infection in a relevant mouse model...

..Little information is available on the incidence, clinical manifestations and epidemiologic features of HCoV-NL infections...

..Unexpectedly, an oseltamivir-resistant A(H1N1) variant containing the H274Y neuraminidase (NA) mutation recently disseminated worldwide, suggesting that the replication and virulence properties of this mutant virus were not compromised...

..Two clades of HBoV were identified. The pathogenic role of HBoV in RTIs is uncertain because it was frequently detected in symptomatic and asymptomatic children and was commonly found with other viruses in symptomatic children...

..The zanamivir-selected variant had a massive deletion in the region encoding the NA active center and an A200T hemagglutinin mutation. This variant exhibited reduced susceptibility to zanamivir with a drug-dependent phenotype...

..Our data indicate that the adjuvanted vaccines tested in this study can elicit stronger, more persistent, and broader immune responses against A/H3N2 strains than nonadjuvanted inactivated influenza vaccines...

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..We sought to evaluate transmission of this mutant virus through the direct contact and the airborne (aerosol and droplet) routes in the ferret model...

..Furthermore, the H274Y mutant strain was transmitted to ferrets. In conclusion, viral fitness of the H274Y pH1N1 isolate is not substantially altered and has the potential to induce severe disease and to disseminate...

..The rate of cytomegalovirus (CMV) mutations conferring ganciclovir resistance was assessed in a trial comparing intravenous ganciclovir and oral valganciclovir for treatment of CMV disease in solid organ transplant (SOT) recipients...

..Group A and genotype GA2 strains were associated with greater severity of hRSV disease than were group B strains...

..Based on plaque size, yield assays, and NA activity, the impaired viral fitness of the E119V mutant was partially restored by the I222V NA mutation...

..Palivizumab is a humanized monoclonal antibody that prevents severe human respiratory syncytial virus (HRSV) infections...

..Moreover, hMPV, compared to other paramyxoviruses and to the human immunodeficiency virus, seems to be more susceptible to HRA- than HRB-derived peptides...

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..The aim of this study was to characterize the role of two HCMV DNA polymerase mutations (K805Q and T821I) found in a ganciclovir- and foscarnet-resistant clinical isolate from an AIDS patient...

..Thus, emergence of CMV UL54 mutations in the absence of UL97 mutations is a rare but possible event that is not necessarily associated with detrimental clinical outcome in solid organ transplant recipients...

..A-322278 decreased mortality rates and lung virus titers significantly more than oseltamivir in mice infected with the NA H274Y mutant when therapy was started 4 h before or even 48 h after infection...

..Given the novel pandemic influenza A(H1N1) (pH1N1) virus and the restricted number of approved anti-influenza drugs, evaluation of potential drug-resistant variants is of high priority...

..These results show, for the first time, the potential of a recombinant plant virus protein to serve as both peptide delivery system and adjuvant in the crucial field of influenza vaccine development...

..8% vs 200-day: 16.1%(1)), the consequence of extending the duration of prophylaxis on the development of viral resistance remains unknown...

..In conclusion, the Q222R reversion mutation compromised Bris07-like H1N1 virus in vitro and in vivo. Thus, the R222Q NA mutation present in the WT virus may have facilitated the emergence of NAI-resistant Bris07 variants...

..Resistance-conferring mutations within the palivizumab binding site occurred in 8.7% of palivizumab recipients and none of the nonrecipients...

..A/H3N2 variability leads to poor vaccine effectiveness when the vaccine strain is not well matched to the circulating virus...

..Compared to hemagglutination inhibition, microneutralization demonstrated a higher level of concordance with RT-PCR (kappa = 0.69 versus kappa = 0.60) and greater sensitivity (83% versus 71%; P = 0.016)...

..HMPV is an important cause of illness in young children with a similar, although less severe, clinical presentation to that of HRSV...

..IM peramivir could constitute an alternative for treatment of oseltamivir-resistant A/H1N1 infections, although additional studies are warranted to support such a recommendation...

..In conclusion, real-time PCR assays aimed at amplifying the N and L genes which are coding for two internal viral proteins appear particularly suitable for hMPV diagnostic...

..In ferrets, however, the mutant strain appears to suffer a delay in its infection of the respiratory tract that allows the susceptible strain to dominate mixed-strain infections...

..Valganciclovir was associated with negligible risk of resistance and thus constitutes a useful alternative to ganciclovir prophylaxis for CMV in high-risk SOT recipients...

..We performed a surveillance study of outpatients who presented with fever and respiratory symptoms to examine the role of viral pathogens in these patients...

..All recombinant viruses containing these unknown mutations were found to be susceptible to ganciclovir...

..Self-isolation only until fever abates appears insufficient to limit transmission. Self-isolation for a week may be more effective, although some case-patients still would shed infectious virus...

..It suggests that certain drug-resistant NA mutants may still be virulent although additional studies using clinical isolates are needed to confirm our results...

..We sought to describe the epidemiological, virological, and histopathological findings associated with a large outbreak of hMPV infection in a long-term care facility...

..In 2009, several countries used the ASO3-adjuvanted pandemic A/H1N1 vaccine. We assessed the persistence of antibody and the priming induced by a single paediatric dose of this vaccine in children...

..Hydroxyurea, a ribonucleotide reductase inhibitor, can increase the activity of nucleoside/nucleotide analogues against drug-resistant viruses...

..We investigated the impact of this mutation in vitro and in animal models using recombinant pH1N1 viruses...

..Resistance to ganciclovir is predominantly associated with alterations in the HCMV UL97 kinase and, more occasionally, with mutations in the HCMV DNA polymerase gene...

..Two infected patients (1 child with leukemia and a 78-year-old woman) died of septic shock and severe pneumonia, respectively...

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..No commercial treatments are yet available for hMPV, although ribavirin has shown activity both in vitro and in animal models. Live attenuated vaccines produced by reverse genetics have also shown good efficacy in animals...

..Until these methods are validated, their methodological limitations should be made explicit and proxy estimates used cautiously in guiding public policy...

..Prior infection with either hMPV or influenza A virus predisposes mice to severe pneumococcus infection...

..Our data demonstrate the risks associated with immunization using inactivated hMPV in this animal model and that this aberrant response should be considered in the development of hMPV vaccines...

..Development of influenza drug resistance is an important problem in immunocompromised children that could result in treatment failure and viral transmission to others...

..Few studies have performed sequential evaluation of the herpes simplex virus (HSV) load using quantitative PCR during episodes of herpes labialis...

..Despite its major effects related to bronchiolitis, pneumonia and its potential role in recurrent wheezing episodes, there is still no commercial treatment or vaccine available against this paramyxovirus...

..We evaluated the effect of pretreatment with Toll-like receptor (TLR) agonists in a mouse model of herpes simplex virus type 1 (HSV-1) encephalitis...

..Human metapneumovirus (hMPV) is associated with acute respiratory tract infections (ARTI) in patients from all age groups...

..Our objective was to assess the prophylactic benefit of a monoclonal antibody (mAb) against the hMPV fusion protein in a murine model...

..These results confirm the potent inhibitory effect of A-315675 against oseltamivir-resistant influenza viruses of the N1 and N2 subtypes and support the clinical development of its bioavailable prodrug A-322278...

..The two methods yielded concordant results for 94.1% of specimens. These tests allowed a thorough etiological assessment of respiratory viruses infecting children in hospital settings and would assist public health interventions...

..CONCLUSIONS: Some thymidine kinase HSV mutants associated with drug resistance may retain their pathogenicity at least in the mouse model described in this study...

..We conclude that, among the influenza virus-negative preselected cases of this study, rhinoviruses were relatively frequent pathogens associated with important respiratory and systemic symptoms...

..These results suggest that the pathogenesis of the two HHV8-associated diseases (i.e., KS and MCD) might be different, as only the latter was associated with important viremia in our patients...

..Our study shows the importance of the HA1 229 residue in virus binding to MDCK cells and confirms the unreliability of cell-based assays in predicting the in vivo susceptibility of HA variants to NAIs...

..This highlights the need for continuous monitoring of resistance markers, as well as the development of new anti-influenza drugs and combination therapies...

..Glucocorticoids (GCs) have not been established as an evidence-based therapy for herpes simplex virus (HSV) encephalitis. We sought to evaluate the effects of early versus delayed GC administration in a model of HSV-1 encephalitis...

..Polyprotein sequence of the Can112051-06 isolate had 91.2% aa identity with Saffold virus; however, EF and CD loops of the viral surface varied substantially...

..In conclusion, hMPV does not cause long-term impairment of pneumococcus lung clearance, in contrast to influenza A virus...

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..There is a need to develop new antiherpetic compounds with different mechanisms of action...

..3% vs. 20.7%). These virological results support the clinical benefit provided by early therapeutic intervention of influenza illness...

..This animal model will be of a great benefit in the evaluation of novel therapeutic and prophylactic modalities...

..The strains were closely related to Australian and American viruses based on analysis of large T antigen (TAg) and VP2 genes. The pathogenic role of WU virus is still uncertain...

..Seroprevalence for HPeVs was 70% in children of < or = 5 years of age and 95% in adults. For children from whom serial sera were sampled, seropositivity increased from 22% to 88% between 2 and 24 months of age...

..Although group A strains predominated, accounting for 69% of all strains, as many B as A strains were found in persons >3 years of age...

..This article presents the current evidence for these and other guidelines for the diagnosis of herpesvirus infections of the CNS...

..These findings suggest that HMPV can be associated with severe lower-respiratory-tract infections in very young children, the elderly, and immunocompromised patients...

..87 nM) viruses. Oseltamivir carboxylate was more active than zanamivir for influenza A(H3N2) isolates (mean IC(50): 0.73 vs. 2.09 nM) whereas it was less potent against B viruses (mean IC(50): 11.53 vs. 4.15 nM)...

..This study highlights the diversity of mechanisms of resistance to oseltamivir in clinical settings, reinforcing the need for novel anti-influenza strategies...

..6%-74.8%, 73.4%-73.6%, and 97.0%-97.1% when compared to HPeV-1, -2, and -3 prototype strains, respectively. Although different, our isolates were closely related; amino acid identity was 99.6%-100% for the last 3 proteins...

..These results confirm animal studies reported elsewhere regarding the genetic stability of influenza M2 mutants and their potential for transmission in humans...

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..This transfer is deviant in mice lacking E(2), which allows pathogens to hide from immune surveillance and exacerbates neuronal damages during viral encephalitis...

..Additional research is needed to define the pathogenesis of this viral infection and the host's specific immune response...

..In contrast, the removal of a positive charge associated with the K805Q change may facilitate access or increase affinity to the adjacent Q807...

..Ribavirin significantly decreased both hMPV replication in lungs (by 5 log10) and global pulmonary inflammation on day 5 postinfection, whereas glucocorticoids reduced only alveolar and interstitial inflammation, compared to controls...

..Because of its recent identification, few multi-year epidemiologic studies of hMPV infection have been reported...

..17 days among patients without recurrence (P=.001). This was not explainable by detectable ganciclovir resistance. CMV load kinetics are useful for identifying, at a very early stage, patients who are more likely to have recurrence...

..We report the case of a young, immunocompromised child who had severe lower respiratory tract infections during two consecutive winter seasons caused by genetically distinct HMPV strains...

..Our data show that fully competent Flu can lead to NF-kappaB-dependent activation of HIV-1 transcription in CD4+ T cells...

..These findings support a previous finding that HMPV is a human respiratory pathogen that merits further study...

..6-fold compared to pre-foscarnet or wild-type isolates) suggesting that adefovir-resistant HSV could be selected in vivo by foscarnet therapy...

..Alterations in both conserved and nonconserved regions of the TK gene were shown to confer high levels of resistance to ACV...

..Twelve specimens (2.3%) were positive by multiple assays. Six specimens yielded HMPV isolates. Four of the 6 isolates were of the uncommon B1 genotype...

..Phylogenetic analysis confirmed the relatedness between Can82853-01 and A308/99 and their divergence from other picornaviruses...

..4%-27.6% at the amino acid level. These results provide evidence for the diversity of both surface glycoproteins of hMPV in Africa, which may be a prerequisite to understanding protective immunity against hMPV...

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..These findings could help explain the frequent emergence and transmission of amantadine-resistant influenza viruses during antiviral pressure in the clinical setting...

..Using a quantitative real-time TaqMan PCR, we analyzed the replication kinetics of hMPV in different cell lines. Our results indicate that hMPV replicates slightly more efficiently in LLC-MK2 than in Vero cells and poorly in HEp-2 cells...

..However, continued vigilance, especially of emerging avian H5N1 strains, combined with careful, systematic laboratory-based monitoring, is essential...