Immunology of Infectious Disease News Volume 3.04 | Feb 4 2015

Class-Switched Memory B Cells Remodel BCRs within Secondary Germinal Centers
The integrated specificity and function of individual memory B cell progeny revealed ongoing evolution of polyclonal antibody specificities through germinal center (GC)-specific transcriptional activity. Researchers demonstrate that vaccine boosts reactivate a cyclic program of GC function in class-switched memory B cells to remodel existing antibody specificities and enhance durable immunological protection. [Nat Immunol] Abstract | Press Release

Dietary Restriction Protects against Experimental Cerebral Malaria via ​Leptin Modulation and T-Cell mTORC1 Suppression
Investigators show that modulation of mouse immunometabolism through brief restriction of food intake (dietary restriction, DR) prevents neuropathology in experimental cerebral malaria. DR reduces mTORC1 activity in T cells, and this effect is abrogated upon ​leptin administration. [Nat Commun] Abstract | Press Release

HIV-1 ​Tat Inhibits Phagocytosis by Preventing the Recruitment of ​Cdc42 to the Phagocytic Cup
Researchers found that extracellular ​Tat, at the subnanomolar concentration present in the sera of HIV-1-infected patients, inhibits the phagocytosis of Mycobacterium avium or opsonized Toxoplasma gondii by human primary macrophages. This inhibition results from a defect in mannose- and Fcγ-receptor-mediated phagocytosis, respectively. [Nat Commun] Abstract

IFN-γ and TNF Are Not Essential Parameters of CD4 T Cell Responses for Vaccine Control of Tuberculosis
Investigators used a mouse model of T cell transfer and aerosolized Mycobacterium tuberculosis infection to assess the contributions of TNF, IFN-γ, and iNOS to vaccine efficacy. [J Infect Dis] Abstract

HIV

HIV-1-Triggered Release of Type I IFN by Plasmacytoid Dendritic Cells Induces BAFF Production in Monocytes
Investigators report that HIV-1 upregulates B cell-activating factor (BAFF) expression and secretion by human monocytes. Moreover, they show that the virus-mediated production of BAFF by monocytes relies on a type I IFN response by a small percentage of plasmacytoid dendritic cells present in the monocyte cultures. [J Immunol] Abstract

Retinoic Acid Imprints a Mucosal-Like Phenotype on Dendritic Cells with an Increased Ability to Fuel HIV-1 Infection
To investigate how the gut microenvironment impacts the ability of dendritic cells (DCs) to drive HIV infection, scientists conditioned human immature monocyte-derived DCs with retinoic acid, before pulsing them with HIV and mixing them with autologous T cells. [J Immunol] Abstract

Nef Promotes Evasion of HIV-1 Infected Cells from the CTLA-4-Mediated Inhibition of T Cell Activation
As HIV-1 infects and replicates in activated CD4⁺ T cells, scientists investigated mechanisms by which HIV-1 modulates CTLA-4 expression to establish productive viral infection in these cells. They demonstrate that HIV-1 infection in activated CD4⁺ T cells was followed by Nef-mediated down-regulation of CTLA-4. [J Gen Virol] Abstract

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Promoter Targeting RNAs: Unexpected Contributors to the Control of HIV-1 Transcription
This review focuses on promoter associated noncoding RNAs, with particular emphasis on their role in determining whether HIV-1 establishes active or latent infection. [Mol Ther Nucleic Acids] Full Article

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PREZCOBIX™ (Darunavir/Cobicistat) Approved in the U.S. for the Treatment of Adults Living with HIV-1
Janssen Therapeutics announced the U.S. Food and Drug Administration has approved PREZCOBIX™ tablets, a human immunodeficiency virus (HIV-1) protease inhibitor combined with a CYP3A4 inhibitor, for the treatment of HIV-1 in combination with other antiretroviral agents for treatment-naive and treatment-experienced adults with no darunavir resistance-associated substitutions. [Janssen Therapeutics] Press Release

U.S. Food and Drug Administration Approves Bristol-Myers Squibb’s Evotaz™ (Atazanavir and Cobicistat) for the Treatment of HIV-1 Infection in Adults
Bristol-Myers Squibb Company announced that the U.S. Food and Drug Administration has approved Evotaz tablets in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults. [Bristol-Myers Squibb Company] Press Release

Novel Concept for HIV and Cancer Vaccines
A team of specialists from the Institute of Biomedical Research at the National Autonomous University of Mexico is developing a vaccine against HIV/AIDS and cancer. An experimental trial has demonstrated success by inducing serum in mice and has been highly neutralizing towards those ailments. [National Autonomous University of Mexico (Medical Xpress)] Press Release

CytoDyn Concludes Phase IIb Study with 98% Success with Four Weeks of Monotherapy – Many HIV Patients in Extension Study with Some Approaching Six Months
CytoDyn Inc. announced that it had concluded its Phase IIb treatment substitution study and reported 39 patients out of 40 participating in the study passed four weeks of monotherapy with PRO 140. [CytoDyn Inc.] Press Release

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