RESEARCH High level of susceptibility to human TRIM5α conferred by HIV-2 capsid sequences

Background: HIV-2, which was transmitted to humans from a distant primate species (sooty mangabey), differs remarkably from HIV-1 in its infectivity, transmissibility and pathogenicity. We have tested the possibility that a greater susceptibility of HIV-2 capsid (CA) to the human restriction factor TRIM5α (hTRIM5α) could contribute to these differences. Results: We constructed recombinant clones expressing CA from a variety of HIV-2 viruses in the context of HIV-1 NL4-3-luciferase. CA sequences were amplified from the plasma of HIV-2 infected patients, including 8 subtype A and 7 subtype B viruses. CA from 6 non-epidemic HIV-2 subtypes, 3 HIV-2 CRF01_AB recombinants and 4 SIVsmm viruses were also tested. Susceptibility to hTRIM5α was measured by comparing single-cycle infectivity in human target cells expressing hTRIM5α to that measured in cells in which hTRIM5α activity was inhibited by overexpression of hTRIM5γ. The insertion of HIV-2 CA sequences in the context of HIV-1 did not affect expression and maturation of the HIV-2 CA protein. The level of susceptibility hTRIM5α expressed by viruses carrying HIV-2 CA sequences was up to 9-fold higher than that of HIV-1 NL4-3 and markedly higher than a panel of primary HIV-1 CA sequences. This phenotype was found both for viruses carrying CA from primary HIV-2 sequences and viruses carrying CA from laboratoryadapte

A longitudinal molecular study of the ecology of malaria infections in free-ranging mandrills

International audienceUnravelling the determinants of host variation in susceptibility and exposure to parasite infections, infection dynamics and the consequences of parasitism on host health is of paramount interest to understand the evolution of complex host-parasite interactions. In this study, we evaluated the determinants, temporal changes and physiological correlates of Plasmodium infections in a large natural population of mandrills (Mandrillus sphinx). Over six consecutive years, we obtained detailed parasitological and physiological data from 100 male and female mandrills of all ages. The probability of infection by Plasmodium gonderi and P. mandrilli was elevated (ca. 40%) but most infections were chronical and dynamic, with several cases of parasite switching and clearance. Positive co-infections also occurred between both parasites. Individual age and sex influenced the probability of infections with some differences between parasites: while P. mandrilli appeared to infect its hosts rather randomly, P. gonderi particularly infected middle-aged mandrills. Males were also more susceptible to P. gonderi than females and were more likely to be infected by this parasite at the beginning of an infection by the simian immunodeficiency virus. P. gonderi, and to a lesser extent P. mandrilli, influenced mandrills' physiology: skin temperatures and neutrophil/lymphocyte ratio were both impacted, generally depending on individual age and sex. These results highlight the ecological complexity of Plasmodium infections in nonhuman primates and the efforts that need to be done to decipher the epidemiology of such parasites

Molecular identification of Mucorales in human tissues: contribution of PCR electrospray-ionization mass spectrometry

International audienceMolecular methods are crucial for mucormycosis diagnosis because cultures are frequently negative, even if microscopy suggests the presence of hyphae in tissues. We assessed PCR/electrospray-ionization mass spectrometry (PCR/ESI-MS) for Mucorales identification in 19 unfixed tissue samples from 13 patients with proven or probable mucormycosis and compared the results with culture, quantitative real-time PCR, 16S-23S rRNA gene internal transcribed spacer region (ITS PCR) and 18S PCR sequencing. Concordance with culture identification to both genus and species levels was higher for PCR/ESI-MS than for the other techniques. Thus, PCR/ESI-MS is suitable for Mucorales identification, within 6 hours, for tissue samples for which microscopy results suggest the presence of hyphae

First next-generation sequencing full-genome characterization of a hepatitis C virus genotype 7 divergent subtype

International audienc

First NGS full genome characterization of a hepatitis C virus genotype 7 divergent subtype.

We report the near full length genome sequence, of an hepatitis C virus isolate from a man originating from Democratic Republic of Congo, whose genotype could not be determined by the routinely used sequence technique.The near-complete genome sequence of this variant BAK1 was obtained by the association of two next generation sequencing technologies.Evolutionary analysis indicates that this isolate BAK1 could be the first reported strain belonging to a new HCV-7b subtype. This new subtype has been incorrectly identified as genotype 2 by Versant HCV Genotype 2.0 assay (LiPA).The requirement of three independent isolates has been filled and a new subtype can be assigned. More examples of HCV-7 are required to better understand its origin, its pathogenicity and its relationship with genotype 2

First NGS full genome characterization of a hepatitis C virus genotype 7 divergent subtype.

We report the near full length genome sequence, of an hepatitis C virus isolate from a man originating from Democratic Republic of Congo, whose genotype could not be determined by the routinely used sequence technique.The near-complete genome sequence of this variant BAK1 was obtained by the association of two next generation sequencing technologies.Evolutionary analysis indicates that this isolate BAK1 could be the first reported strain belonging to a new HCV-7b subtype. This new subtype has been incorrectly identified as genotype 2 by Versant HCV Genotype 2.0 assay (LiPA).The requirement of three independent isolates has been filled and a new subtype can be assigned. More examples of HCV-7 are required to better understand its origin, its pathogenicity and its relationship with genotype 2

Affinity-Purified Respiratory Syncytial Virus Antibodies from Intravenous Immunoglobulin Exert Potent Antibody-Dependent Cellular Cytotoxicity

Mixed infections are one of the major therapeutic challenges, as the current strategies have had limited success. One of the most common and widespread conditions of mixed infection is respiratory syncytial virus-mediated pathology of the respiratory tract in children. There is a dire need for the development of novel therapeutic approaches during mixed infections. Therapeutic intravenous immunoglobulin preparations, obtained from plasma pools of healthy donors have been used in immune deficiencies. This study was thus designed to characterize the functional efficacy of RSV-specific antibodies in IVIg. To explore the functional ability of these affinity-purified RSV-specific antibodies, the antibody-dependent and complement dependent cytotoxicity was determined using peripheral cells of healthy donors. This study demonstrates the existence of highly potent RSV-specific antibodies in IVIg preparations and provides the basis for the use of IVIg as broad-spectrum protective shield to RSV-infected children during mixed infections

A randomised controlled trial to study the transmission of SARS-CoV-2 and other respiratory viruses during indoor clubbing events (ANRS0066s ITOC study)

International audienceBackground: In the context of the circulation of the SARS-CoV-2 B.1.617.2 (Delta) variant, vaccination re-authorised mass indoor gatherings. The "Indoor Transmission of COVID-19" (ITOC) trial (ClinicalTrials.gov, NCT05311865) aimed to assess the risk of transmission of SARS-CoV-2 and other respiratory viruses during an indoor clubbing event among participants fully-vaccinated against COVID-19.Methods: ITOC, a randomised, controlled trial in the Paris region (France), enrolled healthy volunteers aged 18-49 years, fully-vaccinated against COVID-19, with no co-morbidities or symptoms, randomised 1:1 to be interventional group "attendees" or control "non-attendees". The intervention, a 7-hour indoor event in a nightclub at full capacity, with no masking, prior SARS-CoV-2 test result or social distancing required. The primary-outcome measure was the numbers of RT-PCR-determined SARS-CoV-2-positive subjects on self-collected saliva 7 days post-gathering in the per-protocol population. Secondary endpoints focused on 20 other respiratory viruses.Results: Healthy participants (n = 1,216) randomised 2:1 by blocks up to 10, 815 attendees and 401 non-attendees, yielding 529 and 287 subjects, respectively, with day-7 saliva samples. One day-7 sample from each group was positive. Looking at all respiratory viruses together, the clubbing event was associated with an increased risk of infection of 1.59 [95% CI 1.04-2.61].Conclusions: In the context of low Delta-VOC circulation, no evidence of SARS-CoV-2 transmission among asymptomatic and vaccinated participants was found, but the risk of other respiratory virus transmission was higher