# IFN Dependent Control of Acute and Chronic Chikungunya Virus Induced Disease

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $505,745

## Abstract

Abstract
Chikungunya virus (CHIKV) is an emerging mosquito-transmitted alphavirus that causes an abrupt onset of
fever with severe joint and muscle pain. In a significant number of patients chronic and debilitating arthritis can
persists for months to years. CHIKV pathogenesis reflects an interplay between events controlling viral
replication and the host inflammatory immune response. Key mediators of the host response to viral infection
are type I interferons (IFNs), which collectively is comprised of 13 IFN-alpha (α) proteins and single IFN-beta
(β), kappa (κ), epsilon (ε), and omega (ω) proteins. The type I IFN response is known to control CHIKV
infection, as mice lacking the type I IFN receptor (IFNAR) die soon after infection. However, the role of
individual IFN subtypes is poorly understood. In preliminary data, we have found that IFN-β-/- and IRF7-/- (a
surrogate for IFN-α) are more susceptible to CHIKV induced disease, whereas IFN-κ-/- mice are resistant,
providing evidence for functional differences between the IFN subtypes in vivo. In this proposal, we will define
the mechanistic basis for how different type I IFN subtypes modulate CHIKV pathogenesis by exploring their
ability to control viral replication and spread, function as immunomodulatory proteins, or temper the host
response. In Aim 1 we will define the role that IFN-α plays during acute and chronic CHIKV infection by
exploring its ability to limit viral replication and dissemination and determining whether IFN-α regulates the cell
tropism of viral persistence. In Aim 2 we will determine the function of IFN-β during acute and chronic disease
and evaluate its impact on modulating the cellular and adaptive immune response during acute and chronic
infection. In Aim 3 we will investigate the novel actions of IFN-κ by evaluating its impact on CHIKV
pathogenesis in vivo and defining functional differences in signaling through IFNAR between IFN-κ, IFN-α, and
IFN-β. Overall, our studies will provide new insight into the effects of type I IFN immunity on CHIKV induced
disease, which may promote the development of novel therapeutic strategies.

## Key facts

- **NIH application ID:** 9963118
- **Project number:** 5R01AI127513-04
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Michael S Diamond
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $505,745
- **Award type:** 5
- **Project period:** 2017-07-21 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9963118

## Citation

> US National Institutes of Health, RePORTER application 9963118, IFN Dependent Control of Acute and Chronic Chikungunya Virus Induced Disease (5R01AI127513-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9963118. Licensed CC0.

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