Altered Immune Cytokine Expression Associated with KoRV B Infection and Season in Captive Koalas.

Iona E Maher,Damien P Higgins,Peter Prentis

doi:10.1371/journal.pone.0163780

Abstract

Koala (Phascolarctos cinereus) populations are increasingly vulnerable and one of the main threats is chlamydial infection. Koala retrovirus (KoRV) has been proposed as an underlying cause of the koala’s susceptibility to infection with Chlamydia and high rates of lymphoid neoplasia; however, the regionally ubiquitous, endogenous nature of this virus suggests that KoRV A infection is not sufficient for immune suppression to occur. A recently discovered exogenous variant of KoRV, KoRV B, has several structural elements that cause increased pathogenicity in related retroviruses and was associated with lymphoid neoplasia in one study. The present study assesses whether KoRV B infection is associated with alterations in immune function. Cytokine gene expression by mitogen stimulated lymphocytes of KoRV B positive (n = 5–6) and negative (n = 6–7) captive koalas was evaluated by qPCR four times (April 2014-February 2015) to control for seasonal variation. Key immune genes in the Th1 pathway (IFNγ, TNFα), Th2 pathway (IL 10, IL4, IL6) and Th17 pathway (IL17A), along with CD4:CD8 ratio, were assessed. KoRV B positive koalas showed significantly increased up-regulation of IL17A and IL10 in three out of four sampling periods and IFNγ, IL6, IL4 and TNFα in two out of four. IL17A is an immune marker for chlamydial pathogenesis in the koala; increased expression of IL17A in KoRV B positive koalas, and concurrent immune dysregulation, may explain the differences in susceptibility to chlamydial infection and severity of disease seen between individuals and populations. There was also marked seasonal variation in up-regulation for most of the cytokines and the CD4:CD8 ratio. The up-regulation in both Th1 and Th2 cytokines mirrors changes associated with immune dysregulation in humans and felids as a result of retroviral infections. This is the first report of altered immune expression in koalas infected by an exogenous variant of KoRV and also the first report of seasonal variation in cytokine up-regulation and CD4:CD8 ratio in marsupials.

Highlights

Koala (Phascolarctos cinereus) populations are coming under increasing threat, and are listed as vulnerable in all but the southern part of their range [1]
Koala retrovirus (KoRV) has been proposed to be the underlying cause of the propensity of koalas to suffer from chlamydial disease [12,13], as well as the high rates of lymphoid neoplasia seen in koalas [13,14,15,16]
This study reveals that, among captive, KoRV A-positive koalas in temperate latitudes, significant changes to lymphocyte composition and cytokine expression are associated with KoRV B infection and with season

Summary

Introduction

Koala (Phascolarctos cinereus) populations are coming under increasing threat, and are listed as vulnerable in all but the southern part of their range [1]. Climate change, heatwaves, bushfires, motor vehicle accidents, dog attacks and disease [2,3,4,5,6,7,8,9]. The majority of animals infected by KoRV A are apparently healthy and previous authors have suggested that cofactors (potentially including superinfection with exogenous pathogenic KoRV variants, recombination with other retroviruses, interactions with host haplotypes, interaction with somatic mutations or co-infection with other viruses such as herpesvirus) are likely to play a role in disease progression [16]

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