HIV Envelope Leader Peptide Signature and Its Role in Infection
Author Information
Author(s): Asmal Mohammed, Hellmann Ina, Liu Weimin, Keele Brandon F., Perelson Alan S., Bhattacharya Tanmoy, Gnanakaran S., Daniels Marcus, Haynes Barton F., Korber Bette T., Hahn Beatrice H., Shaw George M., Letvin Norman L.
Primary Institution: Beth Israel Deaconess Medical Center, Harvard Medical School
Hypothesis
A signature located in the leader peptide of HIV-1 envelope influences envelope processing and infectivity.
Conclusion
The presence of a histidine or positively charged amino acid at position 12 in the HIV envelope leader peptide is associated with higher envelope expression and increased viral infectivity.
Supporting Evidence
- Histidine at position 12 was more common in acutely transmitted viruses.
- Non-basic residues at position 12 were associated with lower envelope expression.
- Viruses with the position 12 signature had higher infectivity in vitro.
- Envelope incorporation was higher for signature-bearing envelopes.
- Position 12 polymorphisms directly impacted leader peptide efficiency.
Takeaway
This study found that a specific part of the HIV virus helps it spread better when it has certain building blocks, making it more effective at infecting people.
Methodology
The study used HIV envelopes from acutely infected individuals to examine the effects of polymorphisms at position 12 on translation of envelope, leader peptide function, and viral infectivity.
Limitations
The study primarily focused on a specific polymorphism and may not account for other factors influencing HIV infectivity.
Participant Demographics
Participants were acutely infected individuals from whom HIV envelopes were derived.
Statistical Information
P-Value
0.0002
Statistical Significance
p<0.005
Digital Object Identifier (DOI)
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