# Establishing an EcoHIV infected mouse model for the study of platelet activation and microbiome towards an HIV cure

> **NIH NIH R03** · JOHNS HOPKINS UNIVERSITY · 2020 · $122,813

## Abstract

Project Summary
The search for a cure for HIV remains a priority within the scientific community. Key to a cure is an
understanding of the mechanisms underlying the development of latent reservoirs. My ongoing K01 SERCA
work has focused on defining the effect of activated platelets on the development of latent viral reservoirs, with
an emphasis on the sanctuary organ of the brain, through work with in vitro systems and SIV-infected macaque
models. My K01 SERCA data demonstrate that direct interactions with platelets affect monocytes and
endothelium differently, and selective inhibition of platelet-monocyte aggreagates (PMAs) while preserving the
presence of platelet-endothelial associations (PEAs) may be key to effectively controlling the development and
reseeding of latent viral reservoirs. However, parsing apart the mechanisms that mediate these interactions
has proven challenging with the tools currently in my arsenal. To do so, I require an animal model in which 1)
all components of the animal are of a common species origin, allowing for physiologically relevant interactions
between platelets, monocytes, endothelium and other aspects of the immune system, 2) genetic modifications
are feasible, thus allowing for the definition of mechanism through work with animals lacking components of
the pathway of interest, and 3) the animal can be maintained under a variety of conditions, allowing for the
study of environmental influences, such as microbiome, on the mechanisms of interest. The overarching goal
of this R03 proposal is thus to work with the EcoHIV-infected mouse model in my lab to complement and build
upon my ongoing K01-funded macaque and in vitro work. EcoHIV is a chimeric virus in which HIV-1 gp120 has
been replaced with ecotropic murine leukemia virus gp80, conferring specific tropism for mouse cells. EcoHIV
infection in immunocompetent mice mirrors many aspects of HIV pathogenesis, including, as I demonstrate in
my preliminary data, the formation of PMAs. In my first aim, I propose to work with the EcoHIV-infected mouse
to define how platelets interact with monocytes and endothelial cells in the context of HIV, and to determine
how these interactions can be inhibited. This aim will inform a future R01 application to propose targeted
therapeutic interventions to interrup PMAs while preserving PEAs to prevent the establishment of a latent
reservoir in the brain. In my second aim, I hypothesize that platelet activation in HIV infected individuals may
be driven by elements of the gastrointestinal microbiome, and t ultimately the formation of PMAs and/or PEAs.
I will model platelet activation in HIV infection under defined microbial conditions with EcoHIV infected, immune
competent, germ-free mice so that this hypothesis can be tested. This aim will result in a second R01
application to define the elements of the microbiome that drive platelet activation in the context of HIV infection.
Thus this R03 proposal will serve as a critical final ...

## Key facts

- **NIH application ID:** 9842958
- **Project number:** 5R03OD026691-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Kelly Ann Metcalf Pate
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $122,813
- **Award type:** 5
- **Project period:** 2019-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9842958

## Citation

> US National Institutes of Health, RePORTER application 9842958, Establishing an EcoHIV infected mouse model for the study of platelet activation and microbiome towards an HIV cure (5R03OD026691-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9842958. Licensed CC0.

---

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