# Dehydroamino acids in HIV-1 capsid and matrix proteins:  new potential targets for viral inactivation

> **NIH NIH R21** · UNIVERSITY OF WISCONSIN-MADISON · 2024 · $226,590

## Abstract

Project Summary/Abstract
We have recently discovered dehydroamino acids (DHAAs) in the capsid and matrix proteins that make up
HIV-1 virions. These dehydroalanine (DHA) and dehydrobutyrine (DHB) residues result from posttranslational
modification of serine, threonine, or cysteine residues. We propose here to investigate the importance and
origin of these fascinating protein modifications. Their high prevalence in these viral proteins, in marked
contrast to their low levels in the human proteome generally, raises two key questions: a) why are they there?
and b) how did they get there? We hypothesize that DHAAs are present in virions because they play important
roles in the HIV virion assembly or capsid maturation. We hypothesize further that DHAAs are formed by a
presently unknown enzymatic activity in viral or host proteins.
To test these hypotheses, we will conduct mutation and inactivation studies of the amino acids that convert to
dehydroamino acids and study the effects on the viral replication cycle and infectivity. We will use quantitative
proteomics to determine how much of this modification is generated and whether it is before or after viral
maturation. We will seek to discover intra- or intermolecular protein crosslinks, which dehydroamino acids are
known to be able to form, using innovative proteomics approaches. Further, we will seek to discover the
enzyme responsible for the formation of these modifications. The discovery of the enzyme responsible for
DHAA formation would be interesting as fundamental biology, offer new insights into HIV replication, and
potentially reveal a new therapeutic pathway for the treatment of HIV infection.

## Key facts

- **NIH application ID:** 10897262
- **Project number:** 5R21AI179434-02
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** LLOYD M SMITH
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $226,590
- **Award type:** 5
- **Project period:** 2023-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10897262

## Citation

> US National Institutes of Health, RePORTER application 10897262, Dehydroamino acids in HIV-1 capsid and matrix proteins:  new potential targets for viral inactivation (5R21AI179434-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10897262. Licensed CC0.

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