Virologie最新文献

The Human papillomaviruses (HPV) have existed in the human population since the archaic hominids. Over the course of human migration and evolution, HPVs have co-evolved with humans on all continents to become today the leading cause of cervical cancer. HPVs are classified by genera, species, genotype, lineage, sub-lineage and variants. Among more than 200 HPV genotypes, HPV16 is the most common and the most oncogenic at high-risk (HPV-HR). If viral oncogenesis is governed by numerous factors and mechanisms involving the virus and its host, the E6/E7 oncogenic proteins of HR-HPV play a central role and are always expressed in cervical cancers. Those of HPV16 have the greatest affinity for cellular proteins involved in cellular control, p53/E6 and pRb/E7. Some E6/E7 HPV16 mutants are associated with persistent infection, correlating with viral lineages and their ethnic and geographical origin. If the splicing of viral mRNAs encoding E6/E7 allows the overexpression of the E7 protein, which is an essential condition for the establishment of HR-HPV oncogenesis, other mechanisms contribute to strengthening it. On the one hand, the accidental integration of the viral genome, in particular the E1/E2 coding region, participates in the transformation of the infected cell. On the other hand, hypermethylation of the viral L1/L2 genomic regions is observed in the advanced stages of infection. Different methods for analyzing mutations, splice sites, integrations and methylations of the viral genome have been described. These virological markers could complete the detection of HR-HPV in the context of cervical cancer screening, currently recommended in France.

The reverse transcriptase of Moloney Murine Leukemia Virus (MMLV) is an enzyme that synthesizes DNA from an RNA template. Among reverse transcriptases, this enzyme is currently the most commonly used in molecular biology and diagnostics. Since its discovery, this viral protein has been extensively studied, shedding light on its structural and functional characteristics, and offering opportunities to optimize the catalytic performances for biotechnological applications. The review describes the structural motifs of the reverse transcriptase of MMLV, the key amino acids in enzymatic catalysis and the enzyme's properties such as processivity, fidelity and thermal stability. This review reports the optimizations made to improve these parameters, which enabled the modified enzymes to be integrated in the molecular biology tests used in the laboratory on a daily basis.

In medicine, virological diagnosis is mainly based on the detection of the viral genome and antigens, or on the identification of specific antibodies produced in response to infection. These strategies are suitable for characterizing an active infection or past contact with an already known virus. The recent development of tests for evaluating the host's cellular immune response opens new perspectives for personalized patient care based on immunomonitoring. The IGRA tests (Interferon Gamma Release Assay), measuring interferon gamma produced by T lymphocytes stimulated in vitro by antigenic peptides specific to infectious agents, and the quantification of the blood viral load of Torque teno virus (TTV) thus constitute tools for assessing infectious risk, particularly usable to predict opportunistic viral reactivations in immunocompromised patients. The characterization of the expression profile of interferon stimulated genes in a respiratory sample is also likely to provide significant assistance in diagnosis, discriminating a viral infection from a bacterial infection, an acute infection from a persistence of nucleic acids from non replicating microorganisms or allowing, in case of viral emergence, to quickly identify infected subjects in the absence of specific PCR tests available. All of these new approaches, described in this review, have the potential to considerably improve patient care with the objective to correctly prescribe medical virology tests and anti-infective treatments.