Toll-Like Receptor and Cytokine Responses to Infection with Endogenous and Exogenous Koala Retrovirus, and Vaccination as a Control Strategy.

Mohammad Kayesh,Md Hashem,Kyoko Tsukiyama-Kohara

doi:10.3390/cimb43010005

Abstract

Koala populations are currently declining and under threat from koala retrovirus (KoRV) infection both in the wild and in captivity. KoRV is assumed to cause immunosuppression and neoplastic diseases, favoring chlamydiosis in koalas. Currently, 10 KoRV subtypes have been identified, including an endogenous subtype (KoRV-A) and nine exogenous subtypes (KoRV-B to KoRV-J). The host’s immune response acts as a safeguard against pathogens. Therefore, a proper understanding of the immune response mechanisms against infection is of great importance for the host’s survival, as well as for the development of therapeutic and prophylactic interventions. A vaccine is an important protective as well as being a therapeutic tool against infectious disease, and several studies have shown promise for the development of an effective vaccine against KoRV. Moreover, CRISPR/Cas9-based genome editing has opened a new window for gene therapy, and it appears to be a potential therapeutic tool in many viral infections, which could also be investigated for the treatment of KoRV infection. Here, we discuss the recent advances made in the understanding of the immune response in KoRV infection, as well as the progress towards vaccine development against KoRV infection in koalas.

Highlights

The koala (Phascolarctos cinereus), an iconic marsupial of Australia, is facing severe population decline due to man-made hazards and natural infections [1,2]
The understanding of Koala retrovirus (KoRV) is rapidly growing, and in this review we aimed to focus on the recent advances of host–virus interactions, vaccine development, and the investigation of alternative strategies for protecting koala health and conservation
We found a significantly upregulated expression of IL-6 in koala PBMCs infected with two exogenous KoRV subtypes (KoRV-B and KoRV-C) in addition to the endogenous KoRV subtype (KoRV-A) compared to koalas with only the endogenous (KoRV-A) infection; no significant change in expression was observed for CD4, CD8b, IL10, and IL-17A (Figure 2) [84]

Summary

Introduction

The koala (Phascolarctos cinereus), an iconic marsupial of Australia, is facing severe population decline due to man-made hazards and natural infections [1,2]. KoRV gained the interest of many virologists due to its unique feature of existing in both exogenous and endogenous forms, providing a unique opportunity to gain insights into how retroviruses infect their new host and evolve together in the early stages of genome invasion [15]. Hobbs et al reported defective KoRV-D and KoRV-E subtypes in koalas with significant deletions in the gag and pol genes [15]. Epidemiological, immunological, and clinical aspects of KoRV infection in koala populations have been reviewed in several previous studies [2,14,20,22,31,32,33,34,35,36]. The understanding of KoRV is rapidly growing, and in this review we aimed to focus on the recent advances of host–virus interactions, vaccine development, and the investigation of alternative strategies for protecting koala health and conservation

Health Effects of KoRV on Koalas

Innate Immune Response to KoRV Infection in Koalas

Vaccine Response in Koalas against KoRV

Findings

Conclusions