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TitleVSV-Displayed HIV-1 Envelope Identifies Broadly Neutralizing Antibodies Class-Switched to IgG and IgA.
Journal, issue, pagesCell Host Microbe, Vol. 27, Issue 6, Page 963-975.e5, Year 2020
Publish dateJun 10, 2020
AuthorsManxue Jia / Rachel A Liberatore / Yicheng Guo / Kun-Wei Chan / Ruimin Pan / Hong Lu / Eric Waltari / Eva Mittler / Kartik Chandran / Andrés Finzi / Daniel E Kaufmann / Michael S Seaman / David D Ho / Lawrence Shapiro / Zizhang Sheng / Xiang-Peng Kong / Paul D Bieniasz / Xueling Wu /
PubMed AbstractThe HIV-1 envelope (Env) undergoes conformational changes during infection. Broadly neutralizing antibodies (bNAbs) are typically isolated by using soluble Env trimers, which do not capture all Env ...The HIV-1 envelope (Env) undergoes conformational changes during infection. Broadly neutralizing antibodies (bNAbs) are typically isolated by using soluble Env trimers, which do not capture all Env states. To address these limitations, we devised a vesicular stomatitis virus (VSV)-based probe to display membrane-embedded Env trimers and isolated five bNAbs from two chronically infected donors, M4008 and M1214. Donor B cell receptor (BCR) repertoires identified two bNAb lineages, M4008_N1 and M1214_N1, that class-switched to immunoglobulin G (IgG) and IgA. Variants of these bNAbs reconstituted as IgA demonstrated broadly neutralizing activity, and the IgA fraction of M1214 plasma conferred neutralization. M4008_N1 epitope mapping revealed a glycan-independent V3 epitope conferring tier 2 virus neutralization. A 4.86-Å-resolution cryogenic electron microscopy (cryo-EM) structure of M1214_N1 complexed with CH505 SOSIP revealed another elongated epitope, the V2V5 corridor, extending from V2 to V5. Overall, the VSV probe identified bNAb lineages with neutralizing IgG and IgA members targeting distinct sites of HIV-1 Env vulnerability.
External linksCell Host Microbe / PubMed:32315598 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.19 - 4.86 Å
Structure data

21456

6vy2

EMDB-21456, PDB-6vy2:
Cryo-EM structure of M1214_N1 Fab in complex with CH505 TF chimeric SOSIP.664 Env trimer
Method: EM (single particle) / Resolution: 4.86 Å

PDB-6vu2:
M1214_N1 Fab structure
Method: X-RAY DIFFRACTION / Resolution: 2.19 Å

Chemicals

ChemComp-HOH:
WATER

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • human immunodeficiency virus 1
  • homo sapiens (human)
  • human immunodeficiency virus
KeywordsIMMUNE SYSTEM / Antibody / gp120 / Cryo-EM / broadly neutralizing antibody / bNAb / Fab / human immunodeficiency virus / HIV-1 / CH505 / SOSIP / Env

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