Abstract:
:Efforts to prevent human immunodeficiency virus type 1 (HIV-1) infection would benefit from understanding the factors that govern virus neutralization by antibodies. We present a mechanistic model for HIV-1 neutralization that includes both virus and antibody parameters. Variations in epitope integrity on the viral envelope glycoprotein (Env) trimer and Env reactivity to bound antibody influence neutralization susceptibility. In addition, we define an antibody-specific parameter, the perturbation factor (PF), that describes the degree of conformational change in the Env trimer required for a given antibody to bind. Minimally perturbing (low-PF) antibodies can efficiently neutralize viruses with a broad range of Env reactivities due to fast on-rates and high affinity for Env. Highly perturbing (high-PF) antibodies inhibit only viruses with reactive (perturbation-sensitive) Envs, often through irreversible mechanisms. Accounting for these quantifiable viral and antibody-associated parameters helps to predict the observed profiles of HIV-1 neutralization by antibodies with a wide range of potencies.
journal_name
Cell Host Microbejournal_title
Cell host & microbeauthors
Haim H,Salas I,McGee K,Eichelberger N,Winter E,Pacheco B,Sodroski Jdoi
10.1016/j.chom.2013.10.006subject
Has Abstractpub_date
2013-11-13 00:00:00pages
547-58issue
5eissn
1931-3128issn
1934-6069pii
S1931-3128(13)00368-5journal_volume
14pub_type
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