How HIV Changes to Use Different Cell Receptors
Author Information
Author(s): Zhuang Ke, Finzi Andres, Tasca Silvana, Shakirzyanova Madina, Knight Heather, Westmoreland Susan, Sodroski Joseph, Cheng-Mayer Cecilia
Primary Institution: Aaron Diamond AIDS Research Center, New York, New York, United States of America
Hypothesis
An early step in the evolution of tropism switch is the adoption of a less constrained and more 'open' envelope conformation for better CD4 usage.
Conclusion
R5 viruses evolved to become more sensitive to CD4 binding, which correlated with better infection of CD4low cells and changes in neutralization sensitivity.
Supporting Evidence
- R5 viruses became increasingly sensitive to CD4 binding prior to coreceptor switch.
- The study observed significant changes in neutralization sensitivity close to the time of X4 emergence.
- Increased sCD4 sensitivity correlated with better infection of CD4low cells.
Takeaway
HIV can change how it enters cells, and this study shows that it first becomes better at using a specific receptor before switching to another one.
Methodology
The study used R5 SHIV-infected macaques to assess changes in virus sensitivity to CD4 and coreceptor usage over time.
Participant Demographics
Two rapid progressor macaques infected with R5 SHIV.
Statistical Information
P-Value
p<0.05
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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