Revised Mimivirus major capsid protein sequence reveals intron-containing gene structure and extra domain

Background: Acanthamoebae polyphaga Mimivirus (APM) is the largest known dsDNA virus. The viral particle has a nearly icosahedral structure with an internal capsid shell surrounded with a dense layer of fibrils. A Capsid protein sequence, D13L, was deduced from the APM L425 coding gene and was shown to be the most abundant protein found within the viral particle. However this protein remained poorly characterised until now. A revised protein sequence deposited in a database suggested an additional N-terminal stretch of 142 amino acids missing from the original deduced sequence. This result led us to investigate the L425 gene structure and the biochemical properties of the complete APM major Capsid protein. Results: This study describes the full length 3430 bp Capsid coding gene and characterises the 593 amino acids long corresponding Capsid protein 1. The recombinant full length protein allowed the production of a specific monoclonal antibody able to detect the Capsid protein 1 within the viral particle. This protein appeared to be post-translationnally modified by glycosylation and phosphorylation. We proposed a secondary structure prediction of APM Capsid protein 1 compared to the Capsid protein structure of Paramecium Bursaria Chlorella Virus 1, another member of the Nucleo-Cytoplasmic Large DNA virus family. Conclusion: The characterisation of the full length L425 Capsid coding gene of Acanthamoebae polyphaga Mimivirus provides new insights into the structure of the main Capsid protein. The production of a full length recombinant protein will be useful for further structural studies

Ultrastructural Characterization of the Giant Volcano-like Virus Factory of Acanthamoeba polyphaga Mimivirus

Acanthamoeba polyphaga Mimivirus is a giant double-stranded DNA virus defining a new genus, the Mimiviridae, among the Nucleo-Cytoplasmic Large DNA Viruses (NCLDV). We used utrastructural studies to shed light on the different steps of the Mimivirus replication cycle: entry via phagocytosis, release of viral DNA into the cell cytoplasm through fusion of viral and vacuolar membranes, and finally viral morphogenesis in an extraordinary giant cytoplasmic virus factory (VF). Fluorescent staining of the AT-rich Mimivirus DNA showed that it enters the host nucleus prior to the generation of a cytoplasmic independent replication centre that forms the core of the VF. Assembly and filling of viral capsids were observed within the replication centre, before release into the cell cytoplasm where progeny virions accumulated. 3D reconstruction from fluorescent and differential contrast interference images revealed the VF emerging from the cell surface as a volcano-like structure. Its size dramatically grew during the 24 h infectious lytic cycle. Our results showed that Mimivirus replication is an extremely efficient process that results from a rapid takeover of cellular machinery, and takes place in a unique and autonomous giant assembly centre, leading to the release of a large number of complex virions through amoebal lysis

Will CURE trials introduce an uncomfortable revolution in the field of HIV research?

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The burden of HIV experience and care among MSM having an HIV-positive seroconcordant steady partner: a possible research hypothesis. Results from the French VESPA ANRS EN-12 study

International audienceObjectives: Prevention fatigue, relapse into unsafe sex practices and sexual behaviour changes have been reported in the community of men who have sex with men (MSM) since the introduction of highly active antiretroviral therapy. Engaging in a relationship with a seroconcordant partner is perceived by some HIV-positive MSM as an alternative prevention strategy to consistent condom use. This study addresses whether underlying clinical factors exist characterising HIV-positive MSM in seroconcordant stable partnerships, enrolled in the French national cross-sectional survey VESPA ANRS EN-12.Methods The study group comprised 322 HIV-positive MSM in stable relationships for more than 12 months, with a serodiscordant (n=251) or seroconcordant (n=71) steady partner. Clinical and psychosocial factors were analysed for HIV-positive MSM with a seroconcordant steady partner.Results: Multiple adjustment by logistic regression showed that individuals with a seroconcordant steady partner were more likely to have a history of an AIDS-defining event (OR 95% CI 2.0 (1.1 to 3.7), p=0.02) or be diagnosed as HIV positive before 1990 (OR 95% CI 2.2 (1.3 to 3.9), p=0.004). Conversely, HIV-positive MSM experiencing virological success (ie, high treatment adherence and an undetectable viral load) were more likely to have a serodiscordant steady partner (OR 95% CI 0.5 (0.3 to 0.9), p=0.02).Conclusions: Longitudinal studies are required to understand to what extent HIV history might influence partnership choices among HIV-positive MSM. Positive prevention programmes and reinforcement of treatment adherence strategies are needed for this population and their steady sexual partners

Highlights from the 2012 International Symposium on HIV & Emerging Infectious Diseases (ISHEID): from cART management to the search of an HIV cure.

International audienceABSTRACT: The 2012 International Symposium on HIV and Emerging Infectious Diseases (ISHEID) provided a forum for investigators to hear the latest research developments in the clinical management of HIV and HCV infections as well as HIV-1 reservoirs and cure research. Combined anti-retroviral therapy (c-ART) has had a profound impact on the disease prognosis of individuals living with HIV-1 infection. However, although these anti-retroviral regimens are able to reduce plasma viremia to below the limits of detection for sustained periods of time, there is a rapid recrudescence in plasma viremia if treatment is interrupted. Therefore, despite this potent anti-retroviral suppression, HIV-1 is able to persist within the infected individual. The main 2012 ISHEID theme was, hence "searching for an HIV cure". In this report we not only give details on this main topic of the 2012 ISHEID but also summarize what has been discussed in the areas of HIV epidemiology, access to care, antiretroviral therapy management and recent progress in the therapy of HCV infection in patients with HIV

Informal pre-exposure prophylaxis use in France : results from the Flash PrEP survey (2014)

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Reduced delays in time to first HIV consultation after diagnosis in France in the antiretroviral therapy era: the possible role of a free care system.

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