Podcast
Questions and Answers
What is the primary focus of this study regarding HIV-1 infection?
What is the primary focus of this study regarding HIV-1 infection?
- Analyzing the economic impact of HIV-1
- Assessing the interaction between host and viral genomes (correct)
- Investigating the social determinants of HIV-1 transmission
- Developing new antiretroviral therapies
Which of the following data types were used in this study to assess host-virus interactions?
Which of the following data types were used in this study to assess host-virus interactions?
- Geographic location
- HLA genotyping data, viral genome sequences, and viral RNA load (correct)
- Patient's dietary habits
- Social media usage
The study uses average pairwise diversity as a proxy for what?
The study uses average pairwise diversity as a proxy for what?
- Time since infection (correct)
- Viral fitness
- HLA diversity
- Geographic location of the patient
How many HLA/viral-variant pairs showed a signature of immune-driven selection in the genome-wide screen?
How many HLA/viral-variant pairs showed a signature of immune-driven selection in the genome-wide screen?
Of the HLA/viral-variant pairs identified, how many were found to have an effect on viral load (VL)?
Of the HLA/viral-variant pairs identified, how many were found to have an effect on viral load (VL)?
What method was used to validate some of the identified HLA/viral-variant pairs in the study?
What method was used to validate some of the identified HLA/viral-variant pairs in the study?
According to the author summary, how does the human immune system interact with viruses?
According to the author summary, how does the human immune system interact with viruses?
What is the significance of 'protective' HLA class I alleles, such as B*57:01, in the context of HIV infection?
What is the significance of 'protective' HLA class I alleles, such as B*57:01, in the context of HIV infection?
What does the study highlight about the interaction between the viral genome and the immune system?
What does the study highlight about the interaction between the viral genome and the immune system?
Why is it challenging to study the adaptive dynamics of HIV?
Why is it challenging to study the adaptive dynamics of HIV?
How did this study bypass the limitations of requiring longitudinally sampled treatment-naïve sequences?
How did this study bypass the limitations of requiring longitudinally sampled treatment-naïve sequences?
What does 'HLA-dependent selection' refer to in the context of this study?
What does 'HLA-dependent selection' refer to in the context of this study?
Which of the following best describes the role of HLA genes in HIV infection, according to this study?
Which of the following best describes the role of HLA genes in HIV infection, according to this study?
The study found that most of the HIV variants from the 433 significant pairs were found in which proteins?
The study found that most of the HIV variants from the 433 significant pairs were found in which proteins?
What statistical measure was used to adjust for multiple testing when assessing the association between HLA alleles and HIV variants?
What statistical measure was used to adjust for multiple testing when assessing the association between HLA alleles and HIV variants?
What was the strongest HLA/HIV-variant association found in the study?
What was the strongest HLA/HIV-variant association found in the study?
Why were proviral DNA sequences included in the study, and what sensitivity analysis was conducted regarding them?
Why were proviral DNA sequences included in the study, and what sensitivity analysis was conducted regarding them?
What does the study suggest about the use of average pairwise diversity (APD) in HIV research?
What does the study suggest about the use of average pairwise diversity (APD) in HIV research?
This study mentions a limitation regarding the generalizability of the results. What is it?
This study mentions a limitation regarding the generalizability of the results. What is it?
What do the findings suggest about HIV's adaptation to immune pressure?
What do the findings suggest about HIV's adaptation to immune pressure?
What is one potential use of these finding described by the author?
What is one potential use of these finding described by the author?
With what has VL or viral load been associated?
With what has VL or viral load been associated?
One finding within the study was confirmed using which model?
One finding within the study was confirmed using which model?
The study uses which type of binding prediction?
The study uses which type of binding prediction?
Multiple linear regression models showed which trend?
Multiple linear regression models showed which trend?
Flashcards
HLA-HIV interactions
HLA-HIV interactions
Dynamic associations between the viral and human genomes
Viral escape dynamics
Viral escape dynamics
Mutations allowing the evasion of immune recognition
Viral diversity-based method
Viral diversity-based method
A method to screen for interactions across the viral genome.
HLA genes
HLA genes
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HIV mutations
HIV mutations
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Peer Review History Transparency
Peer Review History Transparency
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Average pairwise diversity (APD)
Average pairwise diversity (APD)
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Sample-based analysis
Sample-based analysis
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Longitudinal data
Longitudinal data
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Multivariable logistic regression models
Multivariable logistic regression models
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Diversity-based approach
Diversity-based approach
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Multivariable logistic regressions
Multivariable logistic regressions
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Genome-wide association studies
Genome-wide association studies
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Protective HLA class I alleles
Protective HLA class I alleles
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HLA-dependent effect
HLA-dependent effect
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Study Notes
Using Viral Diversity to Identify HIV-1 Variants
- A novel systematic approach uses average pairwise viral diversity to assess the host-virus interaction, using sequences (n = 4,464), HLA data (n = 1,044), and viral RNA load (VL) measurements (n = 829).
- The systematic screen identified 98 HLA/viral-variant pairs with immune-driven selection, affecting time of infection on HIV amino acid variant presence
- 12 pairs affected VL, 28/58 validated by time-to-event analyses, and 48/92 by HLA-epitope predictions
- This approach investigates virus and cellular immunity interactions, highlighting their evolutionary complexity in shaping viral evolution and pathogenesis.
Author Summary
- An intricate dance occurs between viruses and the immune system, displayed by viral and human genomes. Viral reactions often manifest as escape dynamics
- A novel viral diversity-based method screens for interactions across the viral genome systematically. HIV-1 sequences and human leukocyte antigen (HLA) variants are used
- Time-dependent relationships were found between 98 HLA and viral variant pairs, where 12 affected viral RNA concentration.
- 28 pairs were confirmed by longitudinal time-to-event analyses, and computational predictions were consistent in 48 of HLA molecules.
- Results show how the interaction of viral genomes and immune response shapes viral evolution which offers avenues to study interactions with real-world cross-sectional information.
Introduction
- HIV's rapid evolution and diversity complicates universal vaccine development, with disease progression differing based on host and viral evolution.
- Human Leukocyte Antigen (HLA) genes are consistent indicators of HIV progression. Class I genes (A, B, C) are linked to mutations, for immune evasion through disrupted antigen processing and reduced T cell recognition.
- The HLA Class I provides advantages to the virus in certain scenarios. With conflicting evidence of Class II.
- Research has explored HLA-HIV interactions in ART-naive individuals, linking viral mutations to HLA alleles.
- HLA class I alleles (B*57:01) are associated with lower viral load and slower Progression.
- Most interactions are associations between HIV mutations and HLA alleles in cross-sectional studies, these temporal dynamics remain unclear
- Longitudinal studies have found viral escape within three years post-infection
- Adaptation in the presence or absence of a protective HLA allele differs in speed and frequency
- Applying a viral diversity-based approach enables studying the effects of HLA-associated HIV adaptation using real-world virus samples.
- The data from the Swiss HIV Cohort Study (SHCS) includes a validated viral genetic diversity score (APD)
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