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Review
. 2018 Dec 4:9:2862.
doi: 10.3389/fimmu.2018.02862. eCollection 2018.

Cytokine-Mediated Tissue Injury in Non-human Primate Models of Viral Infections

Cordelia Manickam  1 , Spandan V Shah  1 , Olivier Lucar  1 , Daniel R Ram  1 , R Keith Reeves  1   2
Affiliations
Review

Cytokine-Mediated Tissue Injury in Non-human Primate Models of Viral Infections

Cordelia Manickam et al. Front Immunol. .

Abstract

Viral infections trigger robust secretion of interferons and other antiviral cytokines by infected and bystander cells, which in turn can tune the immune response and may lead to viral clearance or immune suppression. However, aberrant or unrestricted cytokine responses can damage host tissues, leading to organ dysfunction, and even death. To understand the cytokine milieu and immune responses in infected host tissues, non-human primate (NHP) models have emerged as important tools. NHP have been used for decades to study human infections and have played significant roles in the development of vaccines, drug therapies and other immune treatment modalities, aided by an ability to control disease parameters, and unrestricted tissue access. In addition to the genetic and physiological similarities with humans, NHP have conserved immunologic properties with over 90% amino acid similarity for most cytokines. For example, human-like symptomology and acute respiratory syndrome is found in cynomolgus macaques infected with highly pathogenic avian influenza virus, antibody enhanced dengue disease is common in neotropical primates, and in NHP models of viral hepatitis cytokine-induced inflammation induces severe liver damage, fibrosis, and hepatocellular carcinoma recapitulates human disease. To regulate inflammation, anti-cytokine therapy studies in NHP are underway and will provide important insights for future human interventions. This review will provide a comprehensive outline of the cytokine-mediated exacerbation of disease and tissue damage in NHP models of viral infections and therapeutic strategies that can aid in prevention/treatment of the disease syndromes.

Keywords: animal model; cytokines; non-human primates; tissue damage; viral infections.

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Figures

Figure 1
Figure 1
NHP models for viral infections. Representation of NHP models that are used commonly to study human viral infections with respect to the evolutionary divergence from humans. GBV-B, GB virus-B; ZIKV, Zika virus; DENV, Dengue virus; WNV, West Nile virus; EBOV, Ebola virus; SIV, Simian Immunodeficiency virus; SHIV, Simian/Human Immunodeficiency virus; RhCMV, rhesus cytomegalovirus; HEV, Hepatitis E virus; rhLCV, rhesus lymphocryptovirus; SVV, simian varicella virus; CHIK, chikungunya virus, HIV, Human Imunodeficiency virus; HCV, Hepatitis C virus; and HBV, Hepatitis B virus are some of the most common examples for viral studies in NHP.
Figure 2
Figure 2
Cytokine responses and sequelae in viral infections.
See this image and copyright information in PMC

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