Structural studies of T4S systems by electron microscopy

Abstract: Type IV secretion (T4S) systems are large dynamic nanomachines that transport DNA and/or proteins through the membranes of bacteria. Analysis of T4S system architecture is an extremely challenging task taking into account their multi protein organisation and lack of overall global symmetry. Nonetheless the last decade demonstrated an amazing progress achieved by X-ray crystallography and cryo-electron microscopy. In this review we present a structural analysis of this dynamic complex based on recent advances in biochemical, biophysical and structural studies

Contrasted TCRβ diversity of CD8+ and CD8- T cells in rainbow trout.

Teleost fish express highly diverse naive TCRβ (TRB) repertoires and mount strong public and private clonal responses upon infection with pathogens. Fish T cells express typical markers such as CD8, CD4-1 and CD4-2, CD3, CD28 and CTLA4. Fish CD8(+) T cells have been shown to be responsible for antigen-specific cell-mediated cytotoxicity in in vitro systems using histo-compatible effector and target cells. We compare here the complexity of TRB repertoires between FACS sorted CD8(+) and CD8(-) T cells from spleen and pronephros of rainbow trout. In contrast to human, while the TRB repertoire is highly diverse and polyclonal in CD8(+) T cells of naïve fish, it appeared very different in CD8(-) lymphocytes with irregular CDR3 length distributions suggesting a dominance of activated clones already in naïve fish or the presence of non conventional T cells. After infection with a systemic virus, CD8(+) T cells mount a typical response with significant skewing of CDR3 length profiles. The infection also induces significant modifications of the TRB repertoire expressed by the CD8(-) fraction, but for a different set of V/J combinations. In this fraction, the antiviral response results in an increase of the peak diversity of spectratypes. This unusual observation reflects the presence of a number of T cell expansions that rise the relative importance of minor peaks of the highly skewed distributions observed in unchallenged animals. These results suggest that the diversity of TRB expressed by CD8(+) and CD8(-) αβ T cells may be subjected to different regulatory patterns in fish and in mammals

Avian Influenza Virus

Avian influenza is a disease caused by influenza A virus (IAV) that mainly affects domestic poultry but poses a serious zoonotic threat due to direct transmission from poultry to mammals including human beings. While the high pathogenic avian influenza (HPAI) mainly caused by H5 and H7 subtypes of IAVs lead to high mortality, the low pathogenic avian influenza (LPAI) caused by all the 16 haemagglutinin subtypes lead to high production losses. Wild aquatic birds serve as reservoir hosts as the virus cause productive subclinical infections in them. Reported for the first time in 1878 in Italy, the IAVs have so far caused three pandemics in humans. The H5N1 virus currently circulating for over two decades throughout the world has caused outbreaks in over 60 countries including India. LPAI viruses are transmitted amongst terrestrial poultry via respiratory droplets and aerosols and the HPAI viruses are transmitted via faecal route. Pathogenesis of IAVs is markedly different between wild water birds, terrestrial poultry and humans. Clinical diagnosis of AI is very difficult and often confused with other respiratory diseases of poultry. Diagnosis of AI involves isolation, identification and characterization of the virus. Current molecular techniques particularly the RT-PCR and real-time RT-PCR are recommended for rapid AI diagnosis. Effective control programs for avian influenza in poultry farms or its spread between farms can reduce the loss due to the disease by a minimum of 75%. The various control measures along with their advantages and disadvantages are discussed in detail in this chapter

ESX secretion systems: mycobacterial evolution to counter host immunity

International audienceMycobacterium tuberculosis uses sophisticated secretion systems, named 6 kDa early secretory antigenic target (ESAT6) protein family secretion (ESX) systems (also known as type VII secretion systems), to export a set of effector proteins that helps the pathogen to resist or evade the host immune response. Since the discovery of the esx loci during the M. tuberculosis H37Rv genome project, structural biology, cell biology and evolutionary analyses have advanced our knowledge of the function of these systems. In this Review, we highlight the intriguing roles that these studies have revealed for ESX systems in bacterial survival and pathogenicity during infection with M. tuberculosis. Furthermore, we discuss the diversity of ESX systems that has been described among mycobacteria and selected non-mycobacterial species. Finally, we consider how our knowledge of ESX systems might be applied to the development of novel strategies for the treatment and prevention of disease