Immunology of Infectious Disease News Volume 4.10 | Mar 16 2016

Therapeutic and Prophylactic Activity of Itraconazole against Human Rhinovirus Infection in a Murine Model
Researchers investigated whether itraconazole (ICZ) can protect cells from human rhinovirus (HRV)-induced cytotoxicity. The numbers of immune cells, including granulocytes and monocytes, were reduced in bronchoalveolar lavage fluid (BALF) by ICZ administration after HRV1B infection, corresponding to decreased pro-inflammatory cytokine and chemokine levels in BALF. [Sci Rep] Full Article

Experimental Persistent Infection of BALB/c Mice with Small-Colony Variants of Burkholderia pseudomallei Leads to Concurrent Upregulation of PD-1 on T Cells and Skewed Th1 and Th17 Responses
B. pseudomallei appeared to upregulate the expression of PD-1 on T cells to evade host immune responses, which likely facilitates bacterial persistence in the host. [PLoS Negl Trop Dis] Full Article

RSV Pulmonary Infection in Humanized Mice Induces Human Anti-RSV Immune Responses and Pathology
Scientists assessed respiratory syncytial virus (RSV)-specific human innate, humoral and cellular immune responses in humanized mice with functional human CD4⁺ T and B cells that were generated by introduction of HLA class II genes, various human cytokines and human B cell activation factor by adeno-associated vector, followed by engraftment of human hematopoietic stem cells to immunodeficient NOD scid gamma mice. [J Virol] Abstract

Circulating T Follicular Helper Cells Are Associated with Rapid Virological Response in Chronic Hepatitis C Patients Undergoing Peginterferon Therapy
Researchers investigated the role of circulating CXCR5⁺ CD4⁺ T follicular helper cells, CD19⁺ B cells and the associated cytokines in patients with chronic hepatitis C virus infection. [Int Immunopharmacol] Abstract

HIV

Altered Virome and Bacterial Microbiome in Human Immunodeficiency Virus-Associated Acquired Immunodeficiency Syndrome
Researchers characterized the enteric virome and bacterial microbiome in a cohort of Ugandan patients, including HIV-uninfected or HIV-infected subjects and those either treated with anti-retroviral therapy (ART) or untreated. Low peripheral CD4 T cell counts were associated with an expansion of enteric adenovirus sequences and this increase was independent of ART treatment. [Cell Host Microbe]
Abstract | Graphical Abstract | Press Release

SIV Infection-Mediated Changes in Gastrointestinal Bacterial Microbiome and Virome Are Associated with Immunodeficiency and Prevented by Vaccination
Investigators performed a longitudinal study of a vaccine cohort to define the natural history of changes in the fecal metagenome in simian immunodeficiency virus (SIV)-infected monkeys. Matched rhesus macaques were either uninfected or intrarectally challenged with SIV, with a subset receiving the Ad26 vaccine, an adenovirus vector expressing the viral Env/Gag/Pol antigens. [Cell Host Microbe] Abstract | Graphical Abstract

Lower Viral Loads and Slower CD4 Decline in MRKAd5 HIV-1 Vaccinees Expressing Disease-Susceptible HLA-B*58:02
The authors investigated the HLA-specific impact of the MRKAd5 HIV-1 Gag/Pol/Nef vaccine in a subset of the infected Phambili cohort in whom the disease-susceptible HLA-B*58:02 is highly prevalent. [J Infect Dis] Abstract | Full Article

Expansion of Myeloid-Derived Suppressor Cells Promotes Differentiation of Regulatory T Cells in HIV-1⁺ Individuals
Researchers provide evidence that HIV-induced expansion of monocytic myeloid-derived suppressor cells (M-MDSCs) promote the differentiation of Foxp3⁺ regulatory T cells. They observed a dramatic increase in M-MDSC frequencies in the peripheral blood of HIV-1 seropositive (HIV-1⁺) individuals, even in those on antiretroviral therapy with undetectable viremia, when compared to healthy subjects. [AIDS] Abstract

Antibodies Elicited by Multiple Envelope Glycoprotein Immunogens in Primates Neutralize Primary Human Immunodeficiency Viruses (HIV-1) Sensitized by CD4-Mimetic Compounds
Investigators showed that CD4-mimetic compounds sensitize primary HIV-1 to neutralization by antibodies that can be elicited in monkeys and humans within six months by several envelope glycoproteins vaccine candidates, including gp120 monomers. [J Virol] Abstract

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Dissecting How CD4 T Cells Are Lost During HIV Infection
Although the replicative life cycle of HIV within CD4 T cells is understood in molecular detail, less is known about how this human retrovirus promotes the loss of CD4 T lymphocytes. Recent studies have highlighted how abortive infection of resting and thus nonpermissive CD4 T cells in lymphoid tissues triggers a lethal innate immune response against the incomplete DNA products generated by inefficient viral reverse transcription in these cells. [Cell Host Microbe] Abstract

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Antioxidants Improve Lung Immune Markers in HIV-Infected Patients Who Are Immune Non-Responders
Dietary supplementation with zinc and S-adenosylmethionine, an antioxidant, can improve the function of immune cells in the lungs, a small study involving 14 HIV-infected patients indicated. [Press release from Emory University discussing research presented at the 23^rd Conference on Retroviruses and Opportunistic Infections (CROI), Boston] Press Release

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Benitec’s Hepatitis B Therapy Reduces HBV DNA by 98.5% In Vivo
Benitec Biopharma Limited announced that BB-HB-331, a DNA-directed RNA interference therapy targeting the hepatitis B virus (HBV), demonstrates robust and durable suppression of HBV in vivo following a single administration. [Benitec Biopharma Limited] Press Release

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