Transcriptional response of Mexican axolotls to Ambystoma tigrinum virus (ATV) infection

Abstract

BackgroundVery little is known about the immunological responses of amphibians to pathogens that are causing global population declines. We used a custom microarray gene chip to characterize gene expression responses of axolotls (Ambystoma mexicanum) to an emerging viral pathogen, Ambystoma tigrinum virus (ATV).ResultAt 0, 24, 72, and 144 hours post-infection, spleen and lung samples were removed for estimation of host mRNA abundance and viral load. A total of 158 up-regulated and 105 down-regulated genes were identified across all time points using statistical and fold level criteria. The presumptive functions of these genes suggest a robust innate immune and antiviral gene expression response is initiated by A. mexicanum as early as 24 hours after ATV infection. At 24 hours, we observed transcript abundance changes for genes that are associated with phagocytosis and cytokine signaling, complement, and other general immune and defense responses. By 144 hours, we observed gene expression changes indicating host-mediated cell death, inflammation, and cytotoxicity.ConclusionAlthough A. mexicanum appears to mount a robust innate immune response, we did not observe gene expression changes indicative of lymphocyte proliferation in the spleen, which is associated with clearance of Frog 3 iridovirus in adult Xenopus. We speculate that ATV may be especially lethal to A. mexicanum and related tiger salamanders because they lack proliferative lymphocyte responses that are needed to clear highly virulent iridoviruses. Genes identified from this study provide important new resources to investigate ATV disease pathology and host-pathogen dynamics in natural populations.

Water Temperature Affects Susceptibility to Ranavirus

“…Ranaviruses persist and propagate through complex interactions between host cells and immune responses (Grayfer et al 2015). Cotter et al (2008) reported >100 up-and down-regulated genes in A. mexicanum following exposure to ATV. Some proteins that are encoded by FV3 immune evasion genes include vIF-2a, vCARD, and dUPTase (Grayfer et al 2015).…”

Ranavirus Host Immunity and Immune Evasion

“…Consistent with the notion that hosts mount broad infl ammatory responses to ranaviruses, a comprehensive microarray analysis of axolotls ( Ambystoma mexicanum ) infected with the Ambystoma tigrinum virus (ATV) revealed the upregulation of numerous hallmark pro-infl ammatory and innate immune gene components in the spleens and lungs of these animals (Cotter et al 2008 ). These genes included (but were not limited to) phagocytic receptors and intracellular components, cytokine signaling molecules, complement components, NADPH oxidase subunits (myeloid enzyme catalyzing the reactive oxygen antimicrobial response), and myloperoxidase (granulocyte enzyme catalyzing the production of hydrogen peroxide) (Cotter et al 2008 ).…”

“…These genes included (but were not limited to) phagocytic receptors and intracellular components, cytokine signaling molecules, complement components, NADPH oxidase subunits (myeloid enzyme catalyzing the reactive oxygen antimicrobial response), and myloperoxidase (granulocyte enzyme catalyzing the production of hydrogen peroxide) (Cotter et al 2008 ). In contrast to what has been observed in X. laevis infected with FV3 (Morales et al 2010 ;Morales and Robert 2007 ), no lymphocyte proliferation genes were upregulated in response to ATV infections (Cotter et al 2008 ). This lack of an efficient adaptive response in this species may explain why ATV is so lethal to urodels.…”

“…Microarray analysis of axolotls infected with ATV revealed that in addition to a multifaceted infl ammatory gene response, these animals also upregulate expression of multiple antiviral interferon responsive genes (Cotter et al 2008 ). Among the numerous genes elicited by ranavirus infection were Mx1 genes, antiviral helicases, interferon regulatory factors, an IFITM, and a ribonuclease (Cotter et al 2008 ).…”

“…Among the numerous genes elicited by ranavirus infection were Mx1 genes, antiviral helicases, interferon regulatory factors, an IFITM, and a ribonuclease (Cotter et al 2008 ). However, the genes encoding axolotl type I and type III IFN remain to be identifi ed.…”