Immunology of Infectious Disease News Volume 4.17 | May 2 2016

Topoisomerase 1 Inhibition Suppresses Inflammatory Genes and Protects from Death by Inflammation
Investigators identified topoisomerase 1 (Top1) as a positive regulator of RNA polymerase II transcriptional activity at pathogen-induced genes. Depletion or chemical inhibition of Top1 suppressed the host response against Influenza and Ebola viruses as well as bacterial products. [Science]
Abstract | Press Release 1 | Press Release 2

Maternal-Derived Hepatitis B Virus e Antigen Alters Macrophage Function in Offspring to Drive Viral Persistence after Vertical Transmission
Scientists developed a mouse model to study the effect of maternal hepatitis B virus (HBV) infection on HBV persistence in offspring and found that HBV carried by the mother impaired CD8⁺ T cell responses to HBV in her offspring, resulting in HBV persistence. [Immunity] Abstract | Graphical Abstract | Press Release

IRF7 Inhibition Prevents Destructive Innate Immunity—A Target for Nonantibiotic Therapy of Bacterial Infections
Scientists identified the transcription factor interferon regulatory factor 7 (IRF-7), a heterodimer partner of IRF-3, as a target for non–antibiotics-based therapy of bacterial infections. They identified IRF-7 as a target for immunomodulatory therapy. [Sci Transl Med] Abstract | Press Release

Transcriptome Signature for Dampened Th2 Dominance in Acellular Pertussis Vaccine-Induced CD4⁺ T Cell Responses through TLR4 Ligation
Transcriptomics analysis was performed on purified CD4⁺ T cells of control and vaccinated mice after in vitro restimulation with acellular pertussis vaccine antigens. Multiple key factors in T helper (Th) differentiation, including transcription factors, cytokines, and receptors, were identified within the differentially expressed genes. [Sci Rep] Full Article

HIV

Initiation of Immune Tolerance–Controlled HIV gp41 Neutralizing B Cell Lineages
In germline knock-in mice, broadly neutralizing antibody precursors were deleted, with remaining anergic B cells capable of being activated by germline-binding immunogens to make gp41-reactive immunoglobulin M. [Sci Transl Med] Abstract | Press Release

Public T Cell Receptors Confer High-Avidity CD4 Responses to HIV Controllers
To identify the molecular determinants that underlie this response, investigators characterized the T cell receptor (TCR) repertoire directed at Gag293, the most immunoprevalent CD4 epitope in the HIV-1 capsid. Transfer of these TCRs to healthy donor CD4⁺ T cells conferred high antigen sensitivity and polyfunctionality, thus recapitulating key features of the controller CD4 response. [J Clin Invest] Full Article

Modification of the HIV-Specific CD8⁺ T-Cell Response in an HIV Elite Controller after Chikungunya Virus Infection
Researchers evaluated the impact of Chikungunya virus (CHIKV) infection on the quality of the HIV-specific CD8⁺ T-cell (CTL) response in an HIV elite controller. The results showed that the phenotype and function of HIV-specific CTLs were modified in temporal association with an HIV viral load blip that followed CHIKV infection. [AIDS] Abstract

Early CD4⁺ T Cell Responses Are Associated with Subsequent CD8⁺ T Cell Responses to an rAd5-Based Prophylactic Prime-Boost HIV Vaccine Strategy
Scientists hypothesized that the IFN-γ producing cytotoxic CD8⁺ T cell responses could be predicted by early IL-2 producing CD4⁺ helper T cell responses, and evaluated this hypothesis using data from a Phase I/II prophylactic HIV vaccine trial. [PLoS One] Full Article

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Probing Resistance
Boston College microbial systems biologist Tim van Opijnen has been awarded a five-year, $10 million grant by the National Institutes of Health to lead a multidisciplinary team that will study the role of the immune system in the emergence of antibiotic-resistant bacteria. [Boston College] Press Release

Positive CHMP Opinion for CAZ AVI in the EU for Serious Bacterial Infections
AstraZeneca announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has issued a positive opinion, recommending the approval of a new antibiotic, CAZ AVI powder. CAZ AVI is being developed to treat a broad range of Gram-negative bacterial infections that are increasingly resistant to antibiotics. [AstraZeneca] Press Release

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