Using human tissue to study HIV-1 transmission and replication fitness
Research type
Research Study
Full title
Defining how HIV-1 viral genomes impact viral transmission and replication fitness.
IRAS ID
302005
Contact name
Jamie Mann
Contact email
Sponsor organisation
University of Bristol
Duration of Study in the UK
5 years, 0 months, 0 days
Research summary
RNA viruses are an important group of zoonotic agents. During early stages of transmission, the natural host antiviral system uses receptors for surveillance, detection, and to respond to the pathogen. The genetic material (RNA) of these viruses acts like signals to the immune system. As such, viral genomes are under immune-selective pressure, driving viral evolution and diversification. As a countermeasure and to avoid detection, viruses such as HIV-1, Influenza and picornavirus avoid certain immunostimulatory sequence pattern (e.g., CpG) within their genomes. Our recent research studying HIV-1 found that HIV-1 may contravene this general principle. We found HIV-1 transmitted/founder (T/F) viruses (viruses that infect and replicate within a recipient) contained more of these immunostimulatory sequences pattern in their viral genomes compared to non-transmitting HIV variants. Moreover, we identified that T/F virus genomes contained sequence patterns that make them more likely to produce non-functional proteins and defective virus, which could affect how well these viruses can replicate. Based on these observations, we will study:
1. Why HIV-1 T/F viruses, with increased numbers of immunostimulatory sequences in their vRNA, have improved transmission fitness?
2. Understand which sequence pattern is advantageous for HIV transmission and if it affects replication fitness.
3. Determine if the findings in i) and ii), are linked or independent characteristics of T/F viruses.
The potential applications of this research are wide ranging and include gaining important insights into the mechanisms of viral transmission and replication. This could lead to improved virus surveillance strategies, where genomic information could be used as biomarkers for predicting transmission/replication fitness of variants within populations. Just as important, this work could contribute to the development of targeted interventions and therapies for HIV and other RNA viruses.REC name
South Central - Oxford A Research Ethics Committee
REC reference
24/SC/0145
Date of REC Opinion
8 May 2024
REC opinion
Favourable Opinion