Estimated protection against COVID-19 based on predicted neutralisation titres from multiple antibody measurements in a longitudinal cohort, France, April 2020 to November 2021.

BackgroundThe risk of SARS-CoV-2 (re-)infection remains present given waning of vaccine-induced and infection-acquired immunity, and ongoing circulation of new variants.AimTo develop a method that predicts virus neutralisation and disease protection based on variant-specific antibody measurements to SARS-CoV-2 antigens.MethodsTo correlate antibody and neutralisation titres, we collected 304 serum samples from individuals with either vaccine-induced or infection-acquired SARS-CoV-2 immunity. Using the association between antibody and neutralisation titres, we developed a prediction model for SARS-CoV-2-specific neutralisation titres. From predicted neutralising titres, we inferred protection estimates to symptomatic and severe COVID-19 using previously described relationships between neutralisation titres and protection estimates. We estimated population immunity in a French longitudinal cohort of 905 individuals followed from April 2020 to November 2021.ResultsWe demonstrated a strong correlation between anti-SARS-CoV-2 antibodies measured using a low cost high-throughput assay and antibody response capacity to neutralise live virus. Participants with a single vaccination or immunity caused by infection were especially vulnerable to symptomatic or severe COVID-19. While the median reduced risk of COVID-19 from Delta variant infection in participants with three vaccinations was 96% (IQR: 94-98), median reduced risk among participants with infection-acquired immunity was only 42% (IQR: 22-66).ConclusionOur results are consistent with data from vaccine effectiveness studies, indicating the robustness of our approach. Our multiplex serological assay can be readily adapted to study new variants and provides a framework for development of an assay that would include protection estimates.

Impact of pre-graft serology on risk of BKPyV infection post-renal transplantation.

OBJECTIVES: BK polyomavirus-associated nephropathy is a troublesome disease caused by BK polyomavirus (BKPyV) infection in immunocompromised renal graft recipients. There are no effective treatments available, making immunosuppression reduction the only management option. Thus, pre-graft predictive BKPyV replication markers are needed for identification of patients at high risk of viraemia. METHODS: We conducted a retrospective study to assess the correlation between pre-transplantation BKPyV serostatus and post-transplantation incidence of BKPyV infection. Sera from 329 recipients and 222 matched donors were tested for anti-BKPyV antibodies against BKPyV serotypes I and IV by using a virus-like particle-based immunoglobulin G enzyme-linked immunosorbent assay, and BKPyV DNA load was monitored for at least 1 year post-transplantation. RESULTS: Eighty recipients were viruric and 59 recipients were viraemic post-transplantation. In the post-transplantation period, the probability of developing viraemia for serotype I increased from 4.3% for the D-/R+ group to 12.1% for the D+/R+ group, climbing to 37.5% for the D+/R- group (P < 0.05). When calculating recipient mean titres for serotypes I and IV, we observed a clear difference in the proportions of viraemia, decreasing from 50% for mean titres <400 to 13.5% for titres ≥400 (P < 0.001), as well as a higher proportion of presumptive nephropathy (50% versus 23.1%, respectively; P < 0.05). In univariate analysis, this parameter had an odds ratio of 6.41 for the risk of developing post-transplantation BKPyV viraemia (95% confidence interval 3.16-13.07; P < 0.0001). CONCLUSIONS: Determination of both donor and recipient BKPyV seropositivity before transplantation and antibody titre measurements may serve as a predictive tool to manage clinical BKPyV infection by identification of patients at high risk.

BK Polyomavirus bkv-miR-B1-5p: A Stable Micro-RNA to Monitor Active Viral Replication after Kidney Transplantation.

BACKGROUND: Bkv-miR-B1-5p is a viral micro-RNA (miRNA) specifically produced during BK polyomavirus (BKPyV) replication. Recent studies have suggested using bkv-miR-B1-5p as a biomarker to monitor viral infection and predict complications in kidney transplant patients. To identify the technical limitations of this miRNA quantification in biological samples, knowledge of its stability and distribution in the extracellular compartment is necessary. Moreover, a proof of concept for using bkv-miR-B1-5p as a biomarker of active replication in chronic infection is still missing in the published literature. METHODS: The stability of bkv-miR-B1-5p was evaluated in samples derived from cell cultures and in urine from BKPyV-infected kidney transplant recipients. The miRNA was quantified in different fractions of the extracellular compartment, including exosomes, and protein binding was evaluated. Finally, we developed an in vitro model for chronic culture of BKPyV clinical isolates to observe changes in the bkv-miR-B1-5p level during persistent infections. RESULTS: Bkv-miR-B1-5p is a stable biomarker in samples from humans and in vitro experiments. Marginally associated with the exosomes, most of the circulating bkv-miR-B1-5p is bound to proteins, especially Ago2, so the miRNA quantification does not require specific exosome isolation. The bkv-miR-B1-5p level is predictable of viral infectivity, which makes it a potential specific biomarker of active BKPyV replication after kidney transplantation.

BK Polyomavirus Hijacks Extracellular Vesicles for En Bloc Transmission.

Most people are asymptomatic carriers of the BK polyomavirus (BKPyV), but the mechanisms of persistence and immune evasion remain poorly understood. Furthermore, BKPyV is responsible for nephropathies in kidney transplant recipients. Unfortunately, the sole therapeutic option is to modulate immunosuppression, which increases the risk of transplant rejection. Using iodixanol density gradients, we observed that Vero and renal proximal tubular epithelial infected cells release two populations of infectious particles, one of which cosediments with extracellular vesicles (EVs). Electron microscopy confirmed that a single vesicle could traffic tens of viral particles. In contrast to naked virions, the EV-associated particles (eBKPyVs) were not able to agglutinate red blood cells and did not use cell surface sialylated glycans as an attachment factor, demonstrating that different entry pathways were involved for each type of infectious particle. However, we also observed that naked BKPyV and eBKPyV were equally sensitive to neutralization by the serum of a seropositive patient or commercially available polyvalent immunoglobulin preparations, which occurred at a postattachment step, after endocytosis. In conclusion, our work shows a new mechanism that likely plays a critical role during the primary infection and in the persistence, but also the reactivation, of BKPyV.IMPORTANCE Reactivation of BKPyV is responsible for nephropathies in kidney transplant recipients, which frequently lead to graft loss. The mechanisms of persistence and immune evasion used by this virus remain poorly understood, and a therapeutic option for transplant patients is still lacking. Here, we show that BKPyV can be released into EVs, enabling viral particles to infect cells using an alternative entry pathway. This provides a new view of BKPyV pathogenesis. Even though we did not find any decreased sensitivity to neutralizing antibodies when comparing EV-associated particles and naked virions, our study also raises important questions about developing prevention strategies based on the induction or administration of neutralizing antibodies. Deciphering this new release pathway could enable the identification of therapeutic targets to prevent BKPyV nephropathies. It could also lead to a better understanding of the pathophysiology of other polyomaviruses that are associated with human diseases.

Invasive Tracheobronchial Aspergillosis in Critically Ill Patients with Severe Influenza. A Clinical Trial.

Rationale: Invasive tracheobronchial aspergillosis (ITBA) is an uncommon but severe clinical form of invasive pulmonary aspergillosis in which the fungal infection is entirely or predominantly confined to the tracheobronchial tree.Objectives: To analyze the diagnostic and prognostic differences between tracheobronchial aspergillosis and pulmonary aspergillosis without tracheobronchial lesions among patients admitted to the ICU with severe influenza.Methods: This retrospective, observational study included critically ill patients with influenza associated with pulmonary aspergillosis from three hospital ICUs between 2010 and 2019. Patient characteristics and clinical and mycologic data at admission and during ICU stay were collected in a database to evaluate variables in the two groups.Measurements and Main Results: Thirty-five patients admitted to the ICU with severe influenza and pulmonary aspergillosis were included. Ten patients were included in the group with ITBA (n = 10 of 35; 28.6%), and 25 patients were included in the group without ITBA. The group with ITBA comprised more patients with active smoking, diabetes mellitus, and higher severity scores (Simplified Acute Physiology Score II). Ninety-day mortality rates in the groups with and without ITBA were 90% and 44%, respectively (P = 0.02). Moreover, significantly higher serum 1,3-ß-d-glucan and galactomannan and BAL fluid galactomannan concentrations were observed in the group with ITBA compared with the group without ITBA (P < 0.0001, P = 0.003, and P = 0.008, respectively).Conclusions: ITBA was associated with higher severity scores, mortality, and serum and BAL fluid galactomannan and 1,3-ß-d-glucan concentrations than invasive pulmonary aspergillosis without tracheobronchial lesions. ITBA should be systematically researched by bronchoscopic examination in ICU patients with concomitant pulmonary aspergillosis and influenza.Clinical trial registered with www.clinicaltrials.gov (NCT04077697).

Comparison of nasopharyngeal and saliva swabs for the detection of RNA SARS-CoV-2 during mass screening (SALICOV study).

In the context of a second wave of SARS-CoV-2 transmission, the use of saliva sampling has become an issue of real importance. SARS-CoV-2 RNA screening was performed on nasopharyngeal and saliva swabs collected from 501 individuals from residential homes for the elderly. The saliva samples were collected at the same time as the nasopharyngeal samples. Nasopharyngeal samples yielded positive results for 26 individuals, only two of whom also tested positive with saliva swabs. In this context, saliva collected by swabbing the fluid is not an ideal sample.

Synergistic Activity of Clofazimine and Clarithromycin in an Aerosol Mouse Model of Mycobacterium avium Infection.

Infections with nontuberculous mycobacteria (NTM) have a poor prognosis in patients with underlying respiratory diseases. Clofazimine (CFZ) showed both experimental and clinical promising results against clinically relevant NTM. However, there are no data on CFZ in combination with the current recommended treatment; therefore, we aimed to study its in vivo activity in an aerosol mouse model of Mycobacterium avium In an aerosol infection BALB/c mouse model using M. avium strain Chester, we treated 58 mice with four combinations of rifampin (RIF) at 10 mg/kg, CFZ at 25 mg/kg, and clarithromycin (CLR) and ethambutol (EMB) at 100 mg/kg. Treatment efficacy was assessed on the basis of lung CFU counts after 2 (M2) and 4 (M4) months of treatment. At M2, CLR-RIF-EMB was slightly but significantly more efficient than CFZ-RIF-EMB (3.02 ± 0.12 versus 3.55 ± 0.28, respectively, P < 0.01), whereas CLR-CFZ-EMB and CLR-CFZ-RIF-EMB dramatically decreased lung CFU counts by 4.32 and 4.47 log10, respectively, compared to untreated group. At M4, CLR-RIF-EMB was significantly more efficient than CFZ-RIF-EMB (2 ± 0.53 versus 2.66 ± 0.22, respectively, P = 0.01). The addition of CLZ to CLR dramatically decreased the lung CFU count, with CFU counts 5.41 and 5.79 log10 lower in the CLR-CFZ-EMB and CLR-CFZ-RIF-EMB groups, respectively, than in the untreated group. The addition of CFZ to CLR seems to improve the efficacy of CLR as early as M2 and was confirmed at M4. CFZ, in addition to RIF and EMB, on the other hand, is less effective than CLR-RIF-EMB. These results need to be confirmed by similar studies along with CFZ potential for shortening treatment.

Prospective evaluation of a screening algorithm for carbapenemase-producing Enterobacteriaceae.

BACKGROUND: Carbapenemase-producing Enterobacteriaceae (CPE) have become a major public health issue. The objective of the present study was to prospectively assess the analytical performance of a CPE detection algorithm based on phenotypic tests (the screening test) and MALDI-ToF hydrolysis (the confirmatory test). METHODS: Over a 6-month period and based on a disk diffusion method, 74 carbapenem-resistant strains were included in this study. RESULTS: Of the collected isolates, 54 turned out to be negative after phenotypic tests. Hence, 20 strains (including all of the CPEs) were checked with the confirmation test. Seven strains were positive. After molecular biology assessments in a reference center, three of the seven were found to be false positives. The algorithm had a negative predictive value and a sensitivity of 100%, a specificity of 77%, and a positive predictive value of 20%. CONCLUSION: The algorithm has a 24-hour turnaround time and helps to avoid using expensive molecular biology tests; we consider that it can be used on a routine basis for screening clinical strains.

Apolipoprotein(a) inhibits hepatitis C virus entry through interaction with infectious particles.

The development of different cell culture models has greatly contributed to increased understanding of the hepatitis C virus (HCV) life cycle. However, it is still challenging to grow HCV clinical isolates in cell culture. If overcome, this would open new perspectives to study HCV biology, including drug-resistant variants emerging with new antiviral therapies. In this study we hypothesized that this hurdle could be due to the presence of inhibitory factors in patient serum. Combining polyethylene glycol precipitation, iodixanol gradient, and size-exclusion chromatography, we obtained from HCV-seronegative sera a purified fraction enriched in inhibitory factors. Mass spectrometric analysis identified apolipoprotein(a) (apo[a]) as a potential inhibitor of HCV entry. Apo(a) consists of 10 kringle IV domains (KIVs), one kringle V domain, and an inactive protease domain. The 10 KIVs are present in a single copy with the exception of KIV type 2 (KIV2 ), which is encoded in a variable number of tandemly repeated copies, giving rise to numerous apo(a) size isoforms. In addition, apo(a) covalently links to the apolipoprotein B component of a low-density lipoprotein through a disulfide bridge to form lipoprotein(a). Using a recombinant virus derived from the JFH1 strain, we confirmed that plasma-derived and recombinant lipoprotein(a) as well as purified recombinant apo(a) variants were able to specifically inhibit HCV by interacting with infectious particles. Our results also suggest that small isoforms are less inhibitory than the large ones. Finally, we observed that the lipoprotein moiety of HCV lipoviroparticles was essential for inhibition, whereas functional lysine-binding sites in KIV7 , KIV8 , and KIV10 were not required. CONCLUSIONS: Our results identify apo(a) as an additional component of the lipid metabolism modulating HCV infection. (Hepatology 2017;65:1851-1864).

Correction to: The expression of HCV-associated host factors is dependent on the hepatoma cell line used in HCV studies.

In this article, a clone of HepG2 stably expressing CD81 (HepG2-CD81) was used. Unfortunately, after cell line authentication.

A Simple and Reliable Strategy for BK Virus Subtyping and Subgrouping.

BK virus (BKV)-associated diseases in transplant recipients are an emerging issue. However, identification of the various BK virus subtypes/subgroups is a long and delicate process on the basis of currently available data. Therefore, we wanted to define a simple and effective one-step strategy for characterizing all BK virus strains from the VP1 gene sequence. Based on the analysis of 199 available complete DNA VP1 sequences, phylogenetic trees, alignments, and isolated polymorphisms were used to define an effective strategy for distinguishing the 12 different BK virus subtypes/subgroups. Based on the 12 subtypes identified from the 199 complete BKV VP1 sequences (1,089 bp), 60 mutations that can be used to differentiate these various subtypes/subgroups were identified. Some genomic areas were more variable and comprised mutational hot spots. From a subregion of only 100 bp in the VP1 region (1977 through 2076), we therefore constructed an algorithm that enabled rapid determination of all BKV subtypes/subgroups with 99% agreement (197/199) relative to the complete VP1 sequence. We called this domain of the BK viral genome the BK typing and grouping region (BKTGR). Finally, we validated our viral subtype identification process in a population of 100 transplant recipients with 100% efficiency. The new simpler method of BKV subtyping/subgrouping reported here constitutes a useful tool for future studies that will help us to more clearly understand the impact of BKV subtypes/subgroups on diagnosis, infection, and BK virus-associated diseases.

High association of T1858-G1896 precore mutations with impaired base pairing and high hepatitis B virus DNA levels in HBeAg-negative chronically infected patients.

The progression of liver disease in hepatitis B virus (HBV) infection is fostered by active virus replication. Mutations in the basal core promoter (BCP) and precore (PC) regions of the HBV genome are known to have an impact on viral replication. The aim of the present study was to assess the correlation of mutation profiles in the BCP and PC regions with the viral load in HBeAg-negative chronically infected patients. The HBV genotype, BCP/PC mutations, serum HBV DNA levels, and associated serological markers were analyzed in 92 HBeAg-negative chronically infected patients. Sequence analysis of the BCP and PC regions revealed variability of 19% and 24.1%, respectively. This variability was primarily associated with five critical positions (1753, 1762, 1764, 1896 and 1899). An elevated HBV viral load (>20,000 IU/ml) was classically correlated with F2-F4 liver fibrosis, elevated serum alanine aminotransferase levels, 1762/1764 and 1753 combination mutations, and surprisingly, with an 1858T-1896G double mutation that impairs base pairing at the base of the bulge in the ε encapsidation signal. An analysis of covariance confirmed the independent nature of the relationship between the 1858T-1896G double mutation and the HBV viral load. In conclusion, independently of conventional parameters, this study demonstrates that a high serum HBV DNA level was also associated with PC 1858-1896 mutations. These BCP/PC mutations may have important clinical implications as predictive factors for HBV DNA increase.

Bartholinitis due to Aggregatibacter aphrophilus: a case report.

BACKGROUND: Aggregatibacter aphrophilus, a commensal of the oro-pharyngeal flora and member of the HACEK group of organisms, is an uncommonly encountered clinical pathogen. It has already been described as the causative agent of brain abscesses, empyema, meningitis, sinusitis, otitis media, bacteriemia, pneumonia, osteomyelitis, peritonitis, endocarditis and wound infections. Herein we report the first case of bartholinitis due to A. aphrophilus. CASE PRESENTATION: A 33-year-old woman was admitted for a 3-day genital pain without fever and urinary functional signs. The abscess was incised and drained; A. aphrophilus was the only micro-organism that grew from the pus. The patient received no antibiotics; the clinical course was favourable. CONCLUSION: This case highlights the importance of an effective treatment of recurrent bartholinitis such as a cold resection of the gland. It is presented for its rarity.

The association between killer-cell immunoglobulin-like receptor (KIR) and KIR ligand genotypes and the likelihood of BK virus replication after kidney transplantation.

BK virus is a common opportunistic post-transplantation viral infection. Although some risk factors have been studied in this context, the contribution of NK cells has not been assessed in detail. In a group of kidney transplant recipients, we studied the association between (i) the likelihood of BK virus replication during the two-year period after kidney transplantation and (ii) the genotypes of the killer cell immunoglobulin-like receptor (KIR) repertoire and their human leukocyte antigen (HLA) ligands. Other clinical factors (such as defective organ recovery and immunosuppressive treatment) were also assessed. BK virus replication was observed in 43 of the 103 recipients (41%). Patients with BK virus replication in the plasma were more likely to display defective organ recovery in the first seven days post-transplantation. BK virus replication was not associated with Missing KIR ligands. However, BK virus replication was more frequent in patients with responsive NK cells (i.e. when a ligand for activating KIRs was not homozygous in the recipient and present in the donor). Our results suggest that defective organ recovery and the recipient's activating KIR repertoire may be related (depending on HLA ligands present in the couple recipient / donor) to the reactivation of BK virus replication after kidney transplantation.

Different precore/core mutations of hepatitis B interact with, limit, or favor liver fibrosis severity.

BACKGROUND AND AIM: The impact of basal core promoter (BCP) and precore (PC) mutants of the hepatitis B virus (HBV) on liver disease severity remains controversial. The aim of the present study was to screen BCP and PC mutations in 252 HBV surface antigen (HBsAg) positive carriers in France and to assess relationships between these mutations and severe fibrosis. METHODS: Direct sequencing of the precore/core gene was used to detect A1762T/G1764A and G1757A mutations in the BCP and G1896A and G1899A mutations in the PC region. RESULTS: The prevalences of A1762T/G1764A, G1757A, G1896A, and G1899A mutations were 34.1%, 38.7%, 54.9%, and 29.3% (P < 0.001), respectively. The independent predictors of severe fibrosis (≥F3 Metavir) were older age (P < 0.001), male gender (P = 0.012), elevated alanine aminotransferase (P < 0.001), and the double A1762T/G1764A mutant with no other mutations (P = 0.011). Interestingly, the association of the G1899A mutation with the double A1762T/G1764A mutant significantly counteracted the deleterious effect of the sole double A1762T/G1764A mutant (odds ratio [OR] = 0.28 vs. OR = 3.55, respectively, P = 0.028). CONCLUSIONS: Patients with the A1762T/G1764A mutation have a higher risk of severe fibrosis. The G1899A mutation is a protective factor against severe fibrosis that counteracted the deleterious effect of the A1762T/G1764A mutation. Finally, host phenotypic and HBV genotypic markers independently predict fibrosis severity.

Comparative Evaluation of Three Nucleic Acid-Based Assays for BK Virus Quantification.

With the growing importance of BK virus (BKV), effective and efficient screening for BKV replication in plasma and urine samples is very important for monitoring renal transplant and hematopoietic stem cell transplant recipients, who are at increased risk of BKV-associated diseases. However, recent assays proposed by many manufacturers have not been tested, and the available tests have not been standardized. The aim of the present study was to evaluate and compare the performances of three commercially available kits, R-gene, GeneProof, and RealStar, on plasma and urine specimens from patients infected with various genotypes and to determine the correlations with the results from a reference laboratory. A qualitatively excellent global agreement (96.8%) was obtained. RealStar PCR tended to give a higher sensitivity, especially for subtype Ib1 samples. Comparison of 30 plasma samples and 53 urine samples showed a good agreement between the three assays, with Spearman's Rho correlation coefficient values falling between 0.92 and 0.98 (P < 0.001). Moreover, a perfect correlation was obtained for comparison of the assay performances with the AcroMetrix BKV panel (P < 0.001 for all comparisons). According to Bland-Altman analysis, more than 95% (240/249 comparisons) of sample comparisons were situated in the range of the mean ± 2 standard deviations (SD). The greatest variability between assays was observed for 10.2% of subtype Ib2 samples, with differences of >1 log10 copies/ml. In conclusion, this study demonstrated the reliable and comparable performances of the R-gene, GeneProof, and RealStar real-time PCR systems for quantification of BKV in urine and plasma samples. All three real-time PCR assays are appropriate for screening of BKV replication in patients.

X4 Tropic Virus Prediction Is Associated with a Nadir CD4 T-Cell Count below 100 Cells/mm.

OBJECTIVE: The aim of this study was to evaluate tropism prediction performances of three algorithms [geno2pheno false-positive rate 10% (G2P10), position-specific scoring matrix (PSSM) and a combination of the 11/25 and net charge rules] and to investigate the viral and host factors potentially involved in the X4 or R5 prediction in human immunodeficiency virus-1 (HIV-1) patients. METHODS: Viral tropism was determined in 179 HIV-1-infected patients eligible for CCR5 antagonist therapy. HIV-1 RNA or DNA was extracted and amplified for env gp120 sequencing. In parallel, demographic, viral, immunological and clinical determinants were analyzed. RESULTS: According to the G2P10 algorithm, 48 patients harbored X4 or X4R5 virus. The tropism prediction was concordant for 87.7 and 88.2% of samples when comparing G2P10 with PSSM or with a combination of the 11/25 and net charge rules, respectively. X4 prediction was significantly associated with more than 35 amino acids in the V3 domain (p < 0.0001) and loss of an N-linked glycosylation site (p < 0.0001). Of the factors studied, only the nadir CD4 T-cell count was significantly associated with X4 tropism (p = 0.01). CONCLUSION: We determined that the X4 virus detection is closely linked to the nadir CD4 T-cell count below 100 cells/mm(3) that must be taken into account when considering a CCR5 antagonist therapy switch.

Which therapeutic option for hepatitis C virus genotype 1?

OBJECTIVE: Sofosbuvir and simeprevir in combination with standard therapy are now available for the treatment of patients chronically infected with hepatitis C virus (HCV) genotype 1. With boceprevir and telaprevir, four treatment options are, therefore, now available to clinicians. Phase 3 studies conducted with simeprevir and sofosbuvir compared sustained virological response (SVR) data with those obtained with standard combination therapy and did not include a control arm. It is important to quantify the contribution of these molecules compared to the first direct antiviral agents available. MATERIAL AND METHODS: For HCV genotype 1 patients, we performed a literature review and compared all SVR data from phase 3 randomized placebo-controlled trials conducted with these four molecules according to virological characteristics (genotype, viral load) and patient characteristics (IL28B polymorphism, stage of fibrosis). RESULTS: Simeprevir and sofosbuvir provide a net gain in terms of SVR compared to boceprevir and telaprevir except in the case of telaprevir for treatment-naïve HCV genotype 1b patients. Sofosbuvir achieves higher SVR rates than simeprevir except for treatment-naïve IL28B CC patients and naïve HCV genotype 1b patient. Further, simeprevir moderately improve SVR rates compared to telaprevir in treatment-naïve patients with F3-F4 fibrosis and with HCV genotype 1a infection. CONCLUSION: Sofosbuvir and simeprevir greatly improve the virological response rate compared to first-generation protease inhibitors. All of these data may help in guiding the physician's treatment decisions, based on financial constraints and patient characteristics. These data can be easily updated with future treatment and demonstrate the contribution of new treatment regimens to achieve optimal SVR rates.

The expression of HCV-associated host factors is dependent on the hepatoma cell line used in HCV studies.

Chronic infection by hepatitis C virus (HCV) is a major cause of liver cirrhosis and hepatocellular carcinoma. At present, the most commonly used in vitro model of HCV infection is based on hepatoma cell lines. However, they were obtained from different patients and different cancers and/or differ in their characteristics and permissiveness to HCV. HCV infection can be modulated by several host factors, so we compared six different hepatoma cell lines that are used as in vitro models for HCV for some of these host factors: the seven known HCV entry factors, the six best-characterized HCV-associated microRNAs, and the two single-nucleotide polymorphisms near the IL28B gene associated with response to pegylated alpha interferon and ribavirin combination therapy, all assessed by quantitative PCR. We showed that the cell lines, including Huh-7 and Huh-7-derived cells, have different microRNA and HCV entry factor expression profiles as well as different IL28B genotypes. In conclusion, some of the observed differences might explain the differences in permissiveness of the cell lines, but, above all, they raise questions about the reliability of in vitro HCV research data gathered to date.

The value and complexity of studying cellular immunity against BK Polyomavirus in kidney transplant recipients.

BK Polyomavirus is of particular concern for kidney transplant recipients, due to their immunosuppression. This problem is exacerbated by the high effectiveness of antirejection therapies, which also compromise the organism's ability to fight viral infections. The long-term risk is loss of graft function through BKPyV-associated nephropathy (BKPyVAN). The assessment of host immunity and its link to the control of viral infections is a major challenge. In terms of humoral immunity, researchers have highlighted the prognostic value of the pre-transplantation anti-BKPyV immunoglobulin G titer. However, humoral immunity alone does not guarantee viral clearance, and the correlation between the humoral response and the time course of the infection remains weak. In contrast, cellular immunity variables appear to be more closely associated with viral clearance, given that the cellular immune response to the kidney transplant is the main target of immunosuppressive treatments in recipients. However, the assessment of the cellular immune response to BK Polyomavirus is complex, and many details still need to be characterized. Here, we review the current state of knowledge about BKPyV cellular immunity, as well as the difficulties that may be encountered in studying it in kidney transplant recipient. This is an essential area of research for optimizing the management of transplant recipients and minimizing the risks associated with insidious BKPyV disease.