# HIV Interactions In Viral Evolution

> **NIH NIH U54** · SEATTLE CHILDREN'S HOSPITAL · 2020 · $5,014,695

## Abstract

The HIV Interaction in Viral Evolution (HIVE) Center came together a little more than four years ago to
understand, at the atomic, biophysical and evolutionary level, the system interdependency of interacting HIV
macromolecules and their assemblies which shape the HIV life cycle. To accomplish this goal the proposed
program will continue to explore the structural and biophysical interactions of HIV Gag and Gag-Pol polyproteins,
capsid, reverse transcriptase, and integrase and their evolutionary relationships. The Center's research focus
will also extend to cellular factors that inform the structural and macromolecular dynamics of events in reverse
transcription, assembly, and integration. This will include studies on how APOBEC3 proteins suppress reverse
transcription, and the role of LEDGF in guiding viral integration and its contribution to latency in conjunction with
CPSF6. Studies on HIV drug resistance will tie together a genetic and structural perspective, based on mutational
correlations that are due to constraints on protein structural stability and function and which ultimately shape
fitness. The depth of the computational strength of the program is centered on expanding structural, biophysical,
and viral sequencing findings for developing predictive structural models and small molecule probes targeting
viral function. The strength of the Center's biological and computational research will provide insights into the
interrelationships of viral and host mechanisms, enabling discovery of new drug targets and therapeutic
strategies that may ultimately lead to a cure. The HIVE Center comprises a group of highly collaborative
investigators with deep experience in HIV research and well established expertise in structural, biophysical,
biochemical, and computational biology, as well as synthetic chemistry, and virology. They will study the
mechanistic implications of viral and viral-host macromolecular interactions along with the dynamics and the
impacts of the evolution of drug resistance to address relevant biological questions with the following Specific
Aims:
AIM1: Defining HIV polyproteins and their components in retroviral assembly and maturation
AIM 2: Determining HIV-host interactions driving virus reverse transcription and integration
AIM 3: Understanding evolution of antiviral resistance mutations and their biological and biophysical
 implications through studies
AIM 4: Developing and characterizing novel small molecule probes to understand biological function

## Key facts

- **NIH application ID:** 10363014
- **Project number:** 7U54AI150472-10
- **Recipient organization:** SEATTLE CHILDREN'S HOSPITAL
- **Principal Investigator:** Stefan G Sarafianos
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $5,014,695
- **Award type:** 7
- **Project period:** 2012-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10363014

## Citation

> US National Institutes of Health, RePORTER application 10363014, HIV Interactions In Viral Evolution (7U54AI150472-10). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10363014. Licensed CC0.

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