VRC34-Antibody Lineage Development Reveals How a Required Rare Mutation Shapes the Maturation of a Broad HIV-Neutralizing Lineage.

Cell Host & Microbe
Chen-Hsiang ShenPeter D Kwong

Abstract

Rare mutations have been proposed to restrict the development of broadly neutralizing antibodies against HIV-1, but this has not been explicitly demonstrated. We hypothesized that such rare mutations might be identified by comparing broadly neutralizing and non-broadly neutralizing branches of an antibody-developmental tree. Because sequences of antibodies isolated from the fusion peptide (FP)-targeting VRC34-antibody lineage suggested it might be suitable for such rare mutation analysis, we carried out next-generation sequencing (NGS) on B cell transcripts from donor N123, the source of the VRC34 lineage, and functionally and structurally characterized inferred intermediates along broadly neutralizing and poorly neutralizing developmental branches. The broadly neutralizing VRC34.01 branch required the rare heavy-chain mutation Y33P to bind FP, whereas the early bifurcated VRC34.05 branch did not require this rare mutation and evolved less breadth. Our results demonstrate how a required rare mutation can restrict development and shape the maturation of a broad HIV-1-neutralizing antibody lineage.

References

Jul 24, 2002·Nucleic Acids Research·Kazutaka KatohTakashi Miyata
Dec 4, 2003·Journal of Synchrotron Radiation·Paul D AdamsThomas C Terwilliger
Jun 25, 2004·Nucleic Acids Research·Ian W DavisDavid C Richardson
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Aug 1, 2007·Journal of Applied Crystallography·Airlie J McCoyRandy J Read
Aug 17, 2010·Bioinformatics·Robert C Edgar
Oct 13, 2011·Molecular Systems Biology·Fabian SieversDesmond G Higgins
Jun 5, 2012·Nucleic Acids Research·Haim AshkenazyTal Pupko
Jul 12, 2012·Systematic Biology·Daniel H Huson, Celine Scornavacca
Jan 22, 2013·Nature Biotechnology·Brandon J DeKoskyGeorge Georgiou
Feb 21, 2013·Methods in Molecular Biology·Megan F ColeEric A Gaucher
Apr 5, 2013·Nature·Hua-Xin LiaoBarton F Haynes
May 15, 2013·Nucleic Acids Research·Jian YeJames M Ostell
Dec 3, 2013·Journal of Immunological Methods·Marcella Sarzotti-KelsoeDavid C Montefiori
Mar 5, 2014·Nature·Nicole A Doria-RoseJohn R Mascola
May 20, 2015·Nature Immunology·Dennis R Burton, John R Mascola
Jun 23, 2015·Nature Structural & Molecular Biology·Young Do KwonPeter D Kwong
Feb 6, 2016·Nature Protocols·Jonathan R McDanielGeorge Georgiou
Apr 27, 2016·Proceedings of the National Academy of Sciences of the United States of America·Brandon J DeKoskyGeorge Georgiou
Jun 28, 2016·Cell·Cassandra A SimonichJulie Overbaugh
Jan 1, 1997·Methods in Enzymology·Zbyszek Otwinowski, Wladek Minor
Dec 21, 2016·Nature Communications·Martin M CorcoranGunilla B Karlsson Hedestam
Jan 31, 2017·Immunological Reviews·Persephone Borrow, M Anthony Moody
Jan 31, 2017·Immunological Reviews·Peter D KwongLawrence Shapiro
Mar 17, 2017·Science Translational Medicine·Mattia BonsignoriBarton F Haynes
Jul 28, 2017·Proceedings of the National Academy of Sciences of the United States of America·Joyce K HwangFrederick W Alt
Jul 8, 2016·Virus Evolution·Melissa Laird SmithDavey M Smith

❮ Previous
Next ❯

Citations

Oct 30, 2020·Viruses·Christophe CaillatWinfried Weissenhorn
Jun 15, 2021·Frontiers in Public Health·David A SpencerAnn J Hessell

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.