# Virologic determinants of HIV elite control

> **NIH NIH F30** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2020 · $50,520

## Abstract

PROJECT SUMMARY
HIV remains one of the most significant public health threats worldwide. Elite controllers are invaluable study
subjects because they control HIV in the absence of anti-retroviral therapy. The study of elite controllers has
helped elucidate host determinants that promote control of chronic HIV replication. Viral factors that contribute
to elite control, however, remain poorly understood. My
that
Desrosiers,
isolates
these
strains.
hypothesize
expressed
research focuses on individual cases of elite control
are associated with highly unusual genetic features in the HIV genome. Since joining the laboratory of Dr.
I have accumulated data that form the basis of this application. I have recovered replicating HIV
and sequenced full-length viral genomes from three of the eight elite controllers in our cohor t. Two of
HIV genomes display highly unusual features that cause a decrease i n he infectivity of laboratory HIV-1
These features are a long V1 domain in Envelope (Env) and a 2 amino acid deletion in Nef. I
that highly unusual genetic variations in the HIV-1 genome hinder determinants of infectivity
by the virus and/or the host. In Aim #1, will characterize
t
I the long V1 domain in Env that reduces
HIV-1 infectivity. Specifically, I will test whether the reduction in infectivity extends to R5-tropic primary isolates
that belong to Group M, subtypes B and C. I will assess whether such a long V1 domain is sufficient to confer
resistance to broadly neutralizing antibodies directed against the V1/V2 region of Env. Lastly, I will determine
whether a long V1 domain increases the likelihood that HIV-1 isolates become densely O-glycosylated. These
questions will be addressed using the well-established TZM-bl cell infectivity and neutralization assays. In Aim
#2, I will determine whether the 2 amino acid deletion at positions 54 and 55 of Nef not only reduces HIV-1
infectivity but also interferes with T cell surface marker endocytosis and/or activation of resting T cells to
produce IL-2. Specifically, I will introduce the double amino acid deletion into nef of the primary HIV-1 isolate
SF2, and will test whether this double deletion impairs endocytosis of MHC-I, CD4 and/or CD3 on human
Jurkat T cells. I will clone SF2Δ54-55 nef into an SIV backbone that has been modified to express only this
chimeric nef. I will grow rhesus macaque 221 T cells in the absence of IL-2, and will test whether the induction
of IL-2 that follows infection of 221 T cells with SIV is impaired when SIV expresses SF2Δ54-55 Nef in the
absence of endogenous SIV Nef. By studying these highly unusual genetic features in the HIV-1 genomes of
our elite controllers, I expect to shed light on the relative importance and functional role of individual HIV
genetic elements that may contribute to control of chronic HIV-1 infection. Characterization of the mechanisms
by which these genetic variations decrease viral infectivity will likely advance our understanding of viral
persisten...

## Key facts

- **NIH application ID:** 9981618
- **Project number:** 5F30AI134381-03
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Zachary Aaron Silver
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $50,520
- **Award type:** 5
- **Project period:** 2018-08-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9981618

## Citation

> US National Institutes of Health, RePORTER application 9981618, Virologic determinants of HIV elite control (5F30AI134381-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9981618. Licensed CC0.

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