Friend retrovirus studies reveal complex interactions between intrinsic, innate and adaptive immunity

Author:

Dittmer Ulf1,Sutter Kathrin1,Kassiotis George23,Zelinskyy Gennadiy1,Bánki Zoltán4,Stoiber Heribert4,Santiago Mario L5,Hasenkrug Kim J6

Affiliation:

1. Institute for Virology, University Clinics Essen, University of Duisburg-Essen, Virchowstr. 179, 45147 Essen, Germany

2. Retroviral Immunology, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK

3. Department of Medicine, Faculty of Medicine, Imperial College London, St Mary's Hospital, Praed St, Paddington, London W2 1NY, UK

4. Division of Virology, Medical University of Innsbruck, Peter-Mayrstr. 4b, A-6020 Innsbruck, Austria

5. University of Colorado School of Medicine, 12700E 19th Ave, Aurora, CO 80045, USA

6. Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, NIAID, NIH, 903S 4th Street, Hamilton, MT 59840, USA

Abstract

ABSTRACT Approximately 4.4% of the human genome is comprised of endogenous retroviral sequences, a record of an evolutionary battle between man and retroviruses. Much of what we know about viral immunity comes from studies using mouse models. Experiments using the Friend virus (FV) model have been particularly informative in defining highly complex anti-retroviral mechanisms of the intrinsic, innate and adaptive arms of immunity. FV studies have unraveled fundamental principles about how the immune system controls both acute and chronic viral infections. They led to a more complete understanding of retroviral immunity that begins with cellular sensing, production of type I interferons, and the induction of intrinsic restriction factors. Novel mechanisms have been revealed, which demonstrate that these earliest responses affect not only virus replication, but also subsequent innate and adaptive immunity. This review on FV immunity not only surveys the complex host responses to a retroviral infection from acute infection to chronicity, but also highlights the many feedback mechanisms that regulate and counter-regulate the various arms of the immune system. In addition, the discovery of molecular mechanisms of immunity in this model have led to therapeutic interventions with implications for HIV cure and vaccine development.

Funder

DFG

National Institute of Allergy and Infectious Diseases

National Institutes of Health

Austrian Science Fund

Francis Crick Institute

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Microbiology

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