Abstract Defective hepatitis B virus (dHBV) generated from spliced RNA is detected in the sera of HBV-chronic carriers. Our study was designed to determine whether the proportion of dHBV changed ...during the course of infection, and to investigate whether dHBV might interfere with HBV replication. To achieve this, HBV wild-type and dHBV levels were determined by Q-PCR in sera from 56 untreated chronic patients and 23 acute patients, in sequential samples from 4 treated-patients and from liver-humanized mice after HBV infection. The proportion of dHBV was higher in patients with severe compared to null/moderate liver disease or with acute infection. Follow-up showed that the proportion of dHBV increased during disease progression. By contrast, a low and stable proportion of dHBV was observed in the humanized-mouse model of HBV infection. Our results highlight a regulation of the proportion of dHBV during liver disease progression that is independent of interference with viral replication.
BackgroundKaposi sarcoma (KS)–associated herpesvirus (KSHV) subtype depends mostly on patient origin. The current study aimed to assess KSHV diversity in a population of men who have sex with men ...(MSM) living in France.MethodsThe study included 264 patients. In 65 MSM, including 57 human immunodeficiency virus (HIV)–infected men with KS, multicentric Castleman disease, or primary effusion lymphoma and 8 HIV-uninfected men receiving HIV preexposure prophylaxis (PrEP), we performed KSHV typing with K1 open reading frame Sanger and KSHV whole-genome sequencing. In 199 other patients, we performed real-time polymerase chain reaction screening for the new variant.ResultsWe found that 51% of KSHV-strains were subtype C (85% C3), and 33% were subtype A. Four patients with severe KSHV disease (2 with visceral KS, 1 with multicentric Castleman disease, and 1 with primary effusion lymphoma) and 1 asymptomatic PrEP user had a new variant resembling the Ugandan subtype F, but with different K1 open reading frame and KSHV whole-genome sequences and a different epidemiological context (MSM vs African population). Its prevalence was 4.5% in Caucasian MSM, and it was absent in other epidemiological groups.ConclusionsSubtype C predominated among MSM living in France. The new F variant was identified in Caucasian MSM and associated with severe KSHV disease, suggesting that subtype F could be split into F1 and F2 variants. Careful screening for this variant may be required in MSM, given the severe clinical presentation of associated diseases.
We identified an HIV-1 isolate with a 3 base pairs insertion in the 100-105 region of the reverse transcriptase gene (RT) along with a G190E and a V75A mutation. Virus carrying the insertion alone or ...in association with G190A was not infectious. The association of G190E and the 100-105 insertion displayed a high level of resistance to non-nucleoside reverse transcriptase inhibitors; the addition of the insertion to G190E may increase the activity of RT.
BACKGROUND: WBC depletion by filtration may prevent the transmission of HTLV‐I, which requires cell‐to‐cell contact. The removal of HTLV‐I‐infected cells in routinely filtered blood cell components ...was measured.
STUDY DESIGN AND METHODS: The study was conducted in Martinique where systematic screening for HTLV‐I and ‐II and universal leukoreduction are mandatory. HTLV‐I was quantified by use of real‐time PCR in 8 RBC units and 4 PLT concentrates before and after filtration. HTLV‐I proviral load in PBMNCs was determined in five of the eight HTLV‐I‐infected blood donors.
RESULTS: The amount of MNC‐associated HTLV‐I DNA in RBC units before filtration was 21 × 106± 29 × 106 copies (mean ± SD). HTLV‐I was detected in 4 of 8 RBC units after filtration, with a number of copies in the MNC fraction ranging from 20 to 140, following a 4.9 to 5.8 log reduction. Flow cytometry analysis performed in 2 of the filtered RBC units containing detectable HTLV‐I showed suboptimal and out‐of‐range leukoreduction (0.56 × 106 and 1.22 × 106 residual WBCs). HTLV was not detected in filtered RBCs from the blood donor with the highest percentage of HTLV‐I‐infected PBMCs (9%).
CONCLUSION: This study confirms that HTLV‐I‐infected cells can be detected in filtered blood cell components and shows that optimal leukoreduction is critical for HTLV‐I removal.
Abstract Background Due to common routes of transmission, HIV and HBV are frequently found as concomitant infections. The dynamic of liver disease in co-infected patients is important to understand ...for appropriate clinical management. Conflicting data surround the role played by genotype-G HBV (HBV-G) during the course of HIV co-infection. Objectives This study aims to assess, using non-invasive methods, liver disease progression in HIV–HBV genotype-G co-infected patients. Study design Co-infected patients with residual HBV replication ( n = 125) were screened for HBV-G infection by specific real-time PCR. The impact of HBV-G on liver fibrosis progression, as assessed by a non invasive biomarker (Fibrotest), was evaluated first, by a cross sectional analysis comparing fibrosis between HBV-G ( n = 23) and non-G ( n = 55) infected patients and second, by a longitudinal study performed over a 5 year period. Results Selected patients were mostly male (90%), with homogenous characteristics between the HBV-G and non-G infected groups, in terms of age, known duration of HIV disease, immune and virological status and duration of HIV/HBV treatment. HBV-G infected patients were exclusively from Western Europe with homosexual intercourses (83%) as principal risk of transmission. Cross sectional analysis revealed comparable liver disease severity distribution between HBV-G and non-G infected patients. Co-infection with other hepatitis viruses and low CD4-nadir, but not HBV-G co-infection, were associated with a 5-year risk of fibrosis progression. Conclusions This study suggests that HBV-G infection is not significantly associated with a more severe liver disease and does not have a deleterious impact on fibrosis progression in efficiently treated HIV–HBV co-infected patients.
BackgroundPropionibacterium acnes (P. acnes) is an anaerobic, Gram-positive bacteria encountered in inflammatory acne lesions, particularly in the pilosebaceous follicle. P. acnes triggers a strong ...immune response involving keratinocytes, sebocytes and monocytes, the target cells during acne development. Lipoteicoic acid and peptidoglycan induce the inflammatory reaction, but no P. acnes surface protein interacting with Toll-like receptors has been identified. P. acnes surface proteins have been extracted by lithium stripping and shown to induce CXCL8 production by keratinocytes.Methodology and principal findingsFar-western blotting identified two surface proteins, of 24.5- and 27.5-kDa in size, specifically recognized by TLR2. These proteins were characterized, by LC-MS/MS, as CAMP factor 1 devoid of its signal peptide sequence, as shown by N-terminal sequencing. Purified CAMP factor 1 induces CXCL8 production by activating the CXCL8 gene promoter, triggering the synthesis of CXCL8 mRNA. Antibodies against TLR2 significantly decreased the CXCL8 response. For the 27 P. acnes strains used in this study, CAMP1-TLR2 binding intensity was modulated and appeared to be strong in type IB and II strains, which produced large amounts of CXCL8, whereas most of the type IA1 and IA2 strains presented little or no CAMP1-TLR2 binding and low levels of CXCL8 production. The nucleotide sequence of CAMP factor displays a major polymorphism, defining two distinct genetic groups corresponding to CAMP factor 1 with 14 amino-acid changes from strains phylotyped II with moderate and high levels of CAMP1-TLR2 binding activity, and CAMP factor 1 containing 0, 1 or 2 amino-acid changes from strains phylotyped IA1, IA2, or IB presenting no, weak or moderate CAMP1-TLR2 binding.ConclusionsOur findings indicate that CAMP factor 1 may contribute to P. acnes virulence, by amplifying the inflammation reaction through direct interaction with TLR2.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
OBJECTIVES:To examine viral diversity and resistance mutations in different brain areas in cases of HIV-encephalopathy.
DESIGN:Twelve postmortem brain areas from three cases of possible or certain ...HIV-encephalopathy were analyzed.
METHODS:After amplification of the reverse transcriptase and the V3 loop region of the gp120 protein, ultradeep sequencing was performed with Illumina technology. Phylogenetic analysis was performed with Fastree v2.1 using the generalized time-reversible (GTR) model. Identification of resistant viral variants was performed on Geneious software, according to HIV-1 genotypic drug resistance interpretationʼs algorithms, 2018 administered by the French Agency for Research on AIDS and Viral Hepatitis.
RESULTS:Phylogenetic analysis revealed significant inter-regional and intra-regional diversity reflecting persistent HIV-1 viral replication in the different brain areas. Although some cerebral regions shared HIV-variants, most of them harbored a specific HIV-subpopulation reflecting HIV compartmentalization in the central nervous system. Furthermore, proportion and distribution of resistance mutations to nucleoside and non-nucleoside reverse transcriptase inhibitors differed among different brain areas of the same case suggesting that penetration of antiretroviral treatment may differ from one compartment to another.
CONCLUSION:This study, performed with a powerful sequencing technique, confirmed HIV compartmentalization in the central nervous system already shown by classical sequencing, suggesting that there are several reservoirs within the brain.
Abstract
Background
Kaposi sarcoma (KS)–associated herpesvirus (KSHV) subtype depends mostly on patient origin. The current study aimed to assess KSHV diversity in a population of men who have sex ...with men (MSM) living in France.
Methods
The study included 264 patients. In 65 MSM, including 57 human immunodeficiency virus (HIV)–infected men with KS, multicentric Castleman disease, or primary effusion lymphoma and 8 HIV-uninfected men receiving HIV preexposure prophylaxis (PrEP), we performed KSHV typing with K1 open reading frame Sanger and KSHV whole-genome sequencing. In 199 other patients, we performed real-time polymerase chain reaction screening for the new variant.
Results
We found that 51% of KSHV-strains were subtype C (85% C3), and 33% were subtype A. Four patients with severe KSHV disease (2 with visceral KS, 1 with multicentric Castleman disease, and 1 with primary effusion lymphoma) and 1 asymptomatic PrEP user had a new variant resembling the Ugandan subtype F, but with different K1 open reading frame and KSHV whole-genome sequences and a different epidemiological context (MSM vs African population). Its prevalence was 4.5% in Caucasian MSM, and it was absent in other epidemiological groups.
Conclusions
Subtype C predominated among MSM living in France. The new F variant was identified in Caucasian MSM and associated with severe KSHV disease, suggesting that subtype F could be split into F1 and F2 variants. Careful screening for this variant may be required in MSM, given the severe clinical presentation of associated diseases.
We identified a new Kaposi sarcoma–associated herpesvirus F variant in 5 Caucasian men who have sex with men. Careful screening may be required in this population, given the severe clinical presentation of associated diseases in the context of immunosuppression.
OBJECTIVE:Most studies about HIV-1 molecular evolution have shown the lack of viral evolution on effective antiretroviral therapy (ART), although controversial results have been documented. We ...therefore aimed to look for evidence of HIV-1 evolution in patients who initiated ART at the time of primary HIV-1 infection (PHI).
DESIGN:We included retrospectively 20 patients diagnosed at PHI, treated at the time of acute infection and with subsequent effective long-term suppressive ART (HIV viral load <20 copies/ml during at least 5 years without any blips).
METHODS:Longitudinal blood samples were deep sequenced using Illumina Miseq. Drug-resistance-associated mutations were retained at 2% cutoff and interpreted using the latest Agence Nationale de Recherches sur le Sida et les Hépatites Virales resistance algorithm. Viral evolution was established when temporal structure on maximum-likelihood phylogenetic tree and significant change over time of HIV-1 genetic diversity measured as the average pairwise distance was observed.
RESULTS:Emergences or disappearances of drug-resistance-associated mutations were detected in the blood cells during follow-up despite sustained virological control. In all patients, tree topologies showed an absence of segregation between sequences and blood viral populations from all time-points were intermingled. Comparison of the average pairwise distance showed the absence of significant viral diversity at the time of primary infection and afterwards during 5 years of full virological control under ART.
CONCLUSION:Despite a slight variation of minority resistance-associated mutation variants, there was no clear evidence of viral evolution during a prolonged period of time in this population of highly controlled adult patients treated at time of PHI.
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