Early events of HIV-1 infection : can signalling be the next therapeutic target?

Intracellular signaling events are signposts of biological processes, which govern the direction and action of biological activities. Through millions of years of evolution, pathogens, such as viruses, have evolved to hijack host cell machinery to infect their targets and are therefore dependent on host cell signaling for replication. This review will detail our current understanding of the signaling events that are important for the early steps of HIV-1 replication. More specifically, the therapeutic potential of signaling events associated with chemokine coreceptors, virus entry, viral synapses, and post-entry processes will be discussed. We argue that these pathways may represent novel targets for antiviral therapy.

Advances in infection and immunity : from bench to bedside

Following the successful inaugural Lorne Infection and Immunity Conference in 2011, scientists have gathered again on 15–17 February 2012 for a second round of this multidisciplinary international meeting. Sessions covered a range of different topics, including innate and adaptive immune responses to infection, host–pathogen interactions, systems biology, as well as clinical and translational research. Here we summarize some of the main concepts discussed at the meeting and the progress on the development of new therapeutic approaches for the control of infectious diseases.

Influenza A virus infection impairs mycobacteria-specific T cell responses and mycobacterial clearance in the lung during pulmonary coinfection.

Individuals infected with mycobacteria are likely to experience episodes of concurrent infections with unrelated respiratory pathogens, including the seasonal or pandemic circulating influenza A virus strains. We analyzed the impact of influenza A virus and mycobacterial respiratory coinfection on the development of CD8 T cell responses to each pathogen. Coinfected mice exhibited reduced frequency and numbers of CD8 T cells specific to Mycobacterium bovis bacille Calmette-Guérin (BCG) in the lungs, and the IFN-γ CD8 T cell response to BCG-encoded OVA was decreased in the lungs of coinfected mice, when compared with mice infected with BCG alone. Moreover, after 2 wk of infection, mice coinfected with both pathogens showed a significant increase in the number of mycobacteria present in the lung compared with mice infected with BCG only. Following adoptive transfer into coinfected mice, transgenic CD8 T cells specific for OVA257–264 failed to proliferate as extensively in the mediastinal lymph nodes as in mice infected only with BCG-OVA. Also noted was a reduction in the proliferation of BCG-specific CD4 transgenic T cells in mice coinfected with influenza compared with mice infected with BCG alone. Furthermore, phenotypic analysis of CD11c+ dendritic cells from mediastinal lymph nodes of the infected mice showed that coinfection was associated with decreased surface expression of MHC class II and class I. Thus, concurrent pulmonary infection with influenza A virus is associated with decreased MHC expression on dendritic cells, reduced activation of BCG-specific CD4 and CD8 T cells, and impaired clearance of mycobacteria.