# Subtype Differences in HIV-1 Transmitted Founder Viruses

> **NIH NIH F31** · EMORY UNIVERSITY · 2020 · $45,520

## Abstract

Abstract
Studies have shown that there are distinct differences in clinical presentation and transmission rates between
HIV-1 subtype A and C. These differences include an increased rate of disease progression for subtype C
infections vs. subtype A, as well as increased transmission rates associated with subtype C vs. subtype A (2,
3). One key aspect of early HIV-1 infection that has been elucidated is the role of the transmitted-founder (TF)
virus, which is the viral variant that establishes systemic HIV-1 infection. Early events in a new HIV-1 infection,
influenced in particular by the replicative capacity (RC) of the TF virus, have been shown to have a profound
effect on the trajectory of disease (4, 5). While characteristics of TFs compared to non-transmitted (NT) viral
variants have been investigated, the role that the TF phenotype plays in HIV-1 subtype differences has not
been investigated. The purpose of this proposed study is to determine the role that viral phenotypes and the
impact of the host has on the clinical differences observed between subtype A and C HIV-1 infections. Our
hypothesis is that the basis of observed differences in disease progression and transmission rate between
HIV-1 subtype A and subtype C infections is due to different phenotypic properties in the subtype A TF virus
and differing interactions of the TF with the innate immune system. We aim to investigate whether there are
phenotypic differences between the TFs of different subtypes and how the TFs of different subtypes interact
with dendritic cells (DCs) and the associated innate immune system to determine if these factors correlate with
the differences observed between clinical presentation and transmission rates. In our first aim, we will
investigate if viral phenotypes of subtype A and subtype C TFs are associated with the different rates of
disease progression by measuring the replicative capacity (RC) of subtype C TFs vs. subtype A TFs. We will
also investigate the ability of subtype C and subtype A TFs to mediate trans-infection, where DCs carry HIV-1
to CD4 T cells and then transfer the virus through an immune synapse to susceptible CD4 T cells. In the final
part of aim 1, we will compare the level of pre-adaptation in subtype A TFV compared to subtype C TFV to see
if subtype C is able to more efficiently evade the adaptive immune response of the host. Our second aim will
examine whether the differences seen between subtypes can be attributed to different innate immune
responses triggered by interaction of the TF virus with DCs. We will determine this by comparing RNA
expression and secreted molecule profiles from DCs derived from the female reproductive tract (FRT DCs)
after exposure to subtype A or subtype C TFs. Finally, we will examine how FRT DCs pulsed with subtype A or
C TFs stimulate resting CD4 T cells by comparing RNA expression profiles of the CD4 T cells. The outcome of
this research will be a better understanding of early interactions of the ...

## Key facts

- **NIH application ID:** 9991606
- **Project number:** 5F31AI145750-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Samantha Mcinally
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 5
- **Project period:** 2019-07-10 → 2022-07-09

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9991606

## Citation

> US National Institutes of Health, RePORTER application 9991606, Subtype Differences in HIV-1 Transmitted Founder Viruses (5F31AI145750-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9991606. Licensed CC0.

---

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