# Aptamer tools for dissecting HIV-1 capsid function and identifying accessible, biologically relevant interaction surfaces.

> **NIH NIH R56** · UNIVERSITY OF MISSOURI-COLUMBIA · 2022 · $384,037

## Abstract

The HIV-1 capsid core is a dynamic structure that participates in a variety of replication processes. The
mature viral capsid core of HIV-1 is a lattice composed of capsid (CA) protein monomers that are thought to
assemble first into CA dimers, followed by ~250 CA hexamers and 12 CA pentamers. Assembly of CA into these
forms requires conformational flexibility of each CA unit, resulting in the presence of unique, solvent-accessible
binding surfaces associated with each assembly form. Despite significant advances in our understanding of CA,
there are many unresolved questions regarding CA structural dynamics and their impact on viral biology. Recent
work supports the presence of partial Gag hexamers at the edges of the immature hexamer lattice, which could
serve as substrates for proteolytic maturation and contribute to assembly of the Gag hexamer lattice. However,
further study is required to fully understand the order in which immature Gag hexamer lattice assembly occurs
and how it leads to activation of the viral protease, as well as the assembly mechanisms underlying remodeling
of proteolytically cleaved CA into the mature capsid core. In addition, the mature capsid core may also undergo
some degree of remodeling to facilitate reverse transcription, nuclear entry and integration, although the degree
of dissociation required and the location at which dissociation begins remain controversial. Furthermore, we still
do not fully understand the broad spectrum of CA interactions with host proteins and their implications for virus
replication, and previously undescribed interactions and targetable surfaces likely exist. Notably, limited tools
exist for the differentiation of CA assembly states in vivo to assess their contributions to viral replication events.
 Aptamers are structured oligonucleotides that bind to molecular targets and can be selected to discriminate
among very similar proteins, including those with only a single amino acid change or different conformations of
the same protein. We have identified aptamers that specifically bind the HIV-1 CA hexamer lattice, as well as
those that bind both the CA hexamer lattice and the soluble CA hexamer, but not the CA monomer. Several of
these aptamers inhibit HIV replication in cell culture, suggesting that they bind to biologically relevant CA
surfaces. Aptamer-mediated interrogation of these binding sites could provide insights into a variety of replication
mechanisms and interactions, present new strategies for viral inhibition, and identify novel accessible sites to
inform development of therapeutics. Here, we propose to identify key aptamer-CA interactions in vitro and in
vivo, examine the impact of inhibitory aptamers on key events in the HIV replication cycle in vitro and in vivo,
and to identify aptamers with new specificities and functional properties. This work will enable use of these
aptamers as functional tools to better understand HIV biology and the role of CA in HIV replication, ide...

## Key facts

- **NIH application ID:** 10655852
- **Project number:** 1R56AI170068-01A1
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **Principal Investigator:** Margaret J Lange
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $384,037
- **Award type:** 1
- **Project period:** 2022-08-10 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10655852

## Citation

> US National Institutes of Health, RePORTER application 10655852, Aptamer tools for dissecting HIV-1 capsid function and identifying accessible, biologically relevant interaction surfaces. (1R56AI170068-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10655852. Licensed CC0.

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