Altered immune parameters associated with Koala Retrovirus (KoRV) and Chlamydial infection in free ranging Victorian koalas (Phascolarctos cinereus)

Abstract

Koala Retrovirus (KoRV) has been widely speculated to cause immune suppression in koalas ( Phascolarctos cinereus ) and to underlie the koala’s susceptibility to infectious disease, however evidence for immunomodulation is limited. The aim of this study is to determine whether immunophenotypic changes are associated with KoRV infection in free ranging Victorian koalas. qPCR was used to examine mRNA expression for Th1 (IFNγ), Th2-promoting (IL6, IL10) and Th17 (IL17A) cytokines, along with CD4 and CD8 in whole blood of koalas (n = 74) from Mt Eccles and Raymond Island in Victoria, Australia, with and without natural chlamydial infection. KoRV positive koalas had significantly lower levels of IL17A ( p ` 0 . 023 ) and IFNγ ( p = 0 . 044 ) gene expression along with a decreased CD4:CD8 gene expression ratio ( p = 0 . 025 ) compared to negative koalas. No effect of chlamydial infection or combined effect of KoRV and chlamydial infection was detected in these populations. The decreased expression of IFNγ could make KoRV infected koalas more susceptible to persistent chlamydial infection, and a decrease in IL17A could make them more susceptible to gram negative bacterial, fungal and mycobacterial infection; but more tolerant of chlamydial infection.

Koalas vaccinated against Koala retrovirus respond by producing increased levels of interferon-gamma

“…In this cohort of KoRV vaccinated and endogenously infected koalas, a small but significant increase in the expression of IFN-γ at both 4- and 8-weeks post-vaccination was observed, compared to pre-vaccination levels. While the biological impact of such sustained up-regulation is not fully known yet, a recent study showed that KoRV-positive southern (Victorian) koalas had significantly lowered IFN-γ levels compared to KoRV-negative koalas [ 4 ]. The authors of that study argued that such decreased IFN-γ levels may increase susceptibility to Chlamydia and other opportunistic infections in KoRV-positive koalas.…”

“…All northern koalas (Queensland and New South Wales) are thought to be harbour at least KoRV-A, a KoRV subtype which is both endogenous and infectious in these koala populations. KoRV infection has been linked to immune alterations, with infected southern koalas shown to have altered immune profiles [ 4 ] and KoRV-B infected northern koalas shown to possess levels of immune dysregulation [ 5 ]. KoRV has also been linked to increased susceptibility to diseases in koalas [ 6 ].…”

Koala retrovirus epidemiology, transmission mode, pathogenesis, and host immune response in koalas (Phascolarctos cinereus): a review

“…KoRV is closely related genetically to gibbon-ape leukemia virus (GaLV) [ 2 , 4 ], feline leukemia virus (FeLV), and porcine endogenous retrovirus (PERV) [ 3 ]. KoRV has been linked to immunosuppression, chlamydiosis, lymphoma, and leukemia and leads to poor outcomes for infected individuals [ 4 , 7 – 10 ]. Progress in KoRV-related research may therefore shed light on issues that need to be tackled for any retrovirus.…”

“…In a recent study, Maher et al characterized the immune response to KoRV infection and found immunophenotypic changes in free-ranging Victorian koalas with significantly lower levels of IL17A and IFN-γ gene expression accompanying a significantly decreased ratio of CD4:CD8 gene expression relative to that seen in KoRV-negative koalas (Fig. 2 ) [ 10 ]. Decreased levels of IL17A and IFN-γ may render koalas more susceptible to bacterial and chlamydial infections, respectively [ 10 ].…”

“…2 ) [ 10 ]. Decreased levels of IL17A and IFN-γ may render koalas more susceptible to bacterial and chlamydial infections, respectively [ 10 ]. Epitopes on the KoRV envelope protein that can be recognized by antibodies have been identified recently, showing that anti-KoRV IgG can be induced and decrease the viral load of KoRV [ 61 ].…”