Journal
JOURNAL OF VIROLOGY
Volume 79, Issue 17, Pages 11161-11169Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.79.17.11161-11169.2005
Keywords
-
Categories
Funding
- NIAID NIH HHS [AI41420, R01 AI041420] Funding Source: Medline
- NIGMS NIH HHS [R29 GM054787, R01 GM054787, GM54787, GM27367, R01 GM027367] Funding Source: Medline
Ask authors/readers for more resources
Human immunodeficiency virus (HIV) Env-induced fusion is highly temperature dependent. When effector and target cells were coincubated at 37 C, there was a kinetic delay before fusion commenced. When effector and target cells were coincubated for varied times at 23 C, a temperature that does not permit fusion, a temperature-arrested stage was created. Raising temperature to 37 C from the 23 C intermediate eliminated the kinetic delay. Inhibitors (T22, AMD3100, and Sch-C) that block fusion by binding chemokine receptors were added after creating the intermediate so as to assess the extent of engagement between gp120 and chemokine receptors at that stage. For both CXCR4 and CCR5 as coreceptors, increasingly long times of coincubation at 23 C reduced the efficacy of the coreceptor-binding inhibitors in blocking fusion. This implies that an increasing number of ternary Env/CD4/coreceptor complexes form over time at 23 C. It also shows that ternary complex formation has a lower temperature threshold than the downstream steps that include Env folding into a six-helix bundle; this provides an experimental means to separate coreceptor binding by gp120 from the subsequent refolding of gp41 into a six-helix bundle structure. As the time of cell coincubation at 23 C was prolonged, more cells quickly fused upon the raising of the temperature to 37 degrees C, and the increase quantitatively correlated with the greater percentage of fusion that was resistant to drugs. Therefore the pronounced kinetic delay in HIV Env-induced fusion is caused predominantly by the time needed for ternary complexes to form.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available