# Defining the Molecular Determinants of Encephalitic Alphavirus Viremia

> **NIH NIH F32** · UNIVERSITY OF COLORADO DENVER · 2023 · $71,792

## Abstract

PROJECT SUMMARY
This proposal is a comparative study on the development of viremia during encephalitic alphavirus infection
and the innate immune mechanisms that mediate clearance of circulating virus in the time before the specific
antibody response. Eastern- (EEEV) and Venezuelan- (VEEV) equine encephalitis viruses are mosquito-
transmitted zoonoses of high public health concern due to their ability to spill-over into human and equine
populations, causing neurologic disease and mortality for which no specific treatments are available. Endemic
to the Americas, their natural reservoirs are avian (EEEV) and rodent populations (VEEV). Natural
transmission of these and other arboviruses is dependent on the development of a viremia of sufficient
amplitude and duration within vertebrate hosts. And while arboviruses are capable of replicating (and causing
disease) within several vertebrate species, not all hosts support transmission back to the arthropod vector. Yet,
the molecular mechanisms that dictate arboviral viremia in amplifying and “dead-end” hosts are poorly defined.
My preliminary findings have identified interesting contrasts from previous studies in Dr. Morrison's laboratory
on the vascular clearance of arthritogenic alphaviruses. In particular, I found that intravenous-inoculated EEEV
particles are cleared from murine circulation, while VEEV-IAB particles escape vascular clearance. My
preliminary data on EEEV clearance from circulation supports a central role for phagocytic cells in the control
of alphavirus viremia, however, in contrast to arthritogenic alphaviruses, EEEV vascular clearance occurs with
slower kinetics and is independent of class A scavenger receptors (SR). I hypothesize EEEV vascular
clearance is mediated by a non-class A SR expressed on liver KC which recognizes a surface-exposed basic
patch in the viral E2 glycoprotein, and VEEV-IAB escape from clearance is similarly determined by the
absence of a surface-exposed basic residue in E2. Moreover, I hypothesize vascular clearance phenotypes of
EEEV and VEEV are host-species dependent and correlate with the distinct vertebrate hosts that support the
maintenance of these independent viral populations in nature. My proposed studies will: (i) define the host and
viral molecular mechanisms by which EEEV is cleared by a non-class A SR, (ii) assess the fate of EEEV
particles following vascular clearance, (iii) identify biochemical properties of VEEV virions that determine
murine vascular clearance, and (iv) elucidate mechanisms that define viremia in amplifying versus “dead-end”
hosts. The knowledge gained from these studies may help identify risk factors for severe disease and aid the
development of new treatments or vaccines against EEEV and VEEV.

## Key facts

- **NIH application ID:** 10599124
- **Project number:** 5F32AI161866-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Stephanie Ander
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $71,792
- **Award type:** 5
- **Project period:** 2022-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10599124

## Citation

> US National Institutes of Health, RePORTER application 10599124, Defining the Molecular Determinants of Encephalitic Alphavirus Viremia (5F32AI161866-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10599124. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*