Histone Deacetylase 6 Knockout Mice Exhibit Higher Susceptibility to Influenza A Virus Infection
VIRUSES-BASEL
Authors: Zanin, Mark; DeBeauchamp, Jennifer; Vangala, Gowthami; Webby, Richard J.; Husain, Matloob
Abstract
The host innate defence against influenza virus infection is an intricate system with a plethora of antiviral factors involved. We have identified host histone deacetylase 6 (HDAC6) as an anti-influenza virus factor in cultured cells. Consistent with this, we report herein that HDAC6 knockout (KO) mice are more susceptible to influenza virus A/PR/8/1934 (H1N1) infection than their wild type (WT) counterparts. The KO mice lost weight faster than the WT mice and, unlike WT mice, could not recover their original body weight. Consequently, more KO mice succumbed to infection, which corresponded with higher lung viral loads. Conversely, the expression of the critical innate antiviral response genes interferon alpha/beta, CD80, CXCL10 and IL15 was significantly downregulated in KO mouse lungs compared to WT mouse lungs. These data are consistent with the known function of HDAC6 of de-acetylating the retinoic acid inducible gene-I (RIG-I) and activating the host innate antiviral response cascade. Loss of HDAC6 thus leads to a blunted innate response and increased susceptibility of mice to influenza A virus infection.
Association between breast milk fatty acids and HIV-1 transmission through breastfeeding
PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS
Authors: Badiou, S.; Tuaillon, E.; Viljoen, J.; Escudie, J. B.; Cristol, J. P.; Newell, M. L.; de Perre, P. Van; Neveu, D.
Abstract
A residual mother-to-child transmission of HIV through breastfeeding persists despite prophylaxis. We identified breast milk fatty acids (FA) associated with postnatal HIV transmission through breastfeeding in a case-control study. Cases (n=23) were HIV-infected women with an infant who acquired HIV after 6 weeks of age. Controls (n=23) were matched on infant's age at sample collection. Adjusting for maternal antenatal plasma CD4 T cell count, cis-vaccenic acid (18:1n-7) and eicosatrienoic acid (20:3n-3) were associated with HIV transmission in opposite dose-response manner: OR (tertile 3 versus tertile 1): 10.8 and 0.16, p for trend= 0.02 and 0.03, respectively. These fatty acids correlated with HIV RNA load, T helper-1 related cytokines, IL15, IP10, and beta 2 microglobulin, positively for cis-vaccenic acid, negatively for eicosatrienoic acid. These results suggested a change in FA synthesis by mammary gland cells leading to increased cis-vaccenic acid in milk of mothers who transmitted HIV to their infant during breastfeeding. (C) 2015 Elsevier Ltd. All rights reserved.