Initial antibodies binding to HIV-1 gp41 in acutely infected subjects are polyreactive and highly mutated.
Abstract
The initial antibody response to HIV-1 is targeted to envelope (Env) gp41, and is
nonneutralizing and ineffective in controlling viremia. To understand the origins
and characteristics of gp41-binding antibodies produced shortly after HIV-1 transmission,
we isolated and studied gp41-reactive plasma cells from subjects acutely infected
with HIV-1. The frequencies of somatic mutations were relatively high in these gp41-reactive
antibodies. Reverted unmutated ancestors of gp41-reactive antibodies derived from
subjects acutely infected with HIV-1 frequently did not react with autologous HIV-1
Env; however, these antibodies were polyreactive and frequently bound to host or bacterial
antigens. In one large clonal lineage of gp41-reactive antibodies, reactivity to HIV-1
Env was acquired only after somatic mutations. Polyreactive gp41-binding antibodies
were also isolated from uninfected individuals. These data suggest that the majority
of gp41-binding antibodies produced after acute HIV-1 infection are cross-reactive
responses generated by stimulating memory B cells that have previously been activated
by non-HIV-1 antigens.
Type
Journal articleSubject
AdultCell Lineage
Female
HIV Antibodies
HIV Envelope Protein gp41
HIV-1
Humans
Male
Mutation
Phylogeny
Plasma Cells
Sequence Analysis, DNA
Viral Load
Viremia
Permalink
https://hdl.handle.net/10161/14733Published Version (Please cite this version)
10.1084/jem.20110363Publication Info
(2011). Initial antibodies binding to HIV-1 gp41 in acutely infected subjects are polyreactive
and highly mutated. J Exp Med, 208(11). pp. 2237-2249. 10.1084/jem.20110363. Retrieved from https://hdl.handle.net/10161/14733.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
Collections
More Info
Show full item recordScholars@Duke
S. Munir Alam
Professor in Medicine
Research Interests.
The Alam laboratory’s primary research is focused on understanding the biophysical
properties of antigen-antibody binding and the molecular events of early B cell activation
using the HIV-1 broadly neutralizing antibody (bnAb) lineage models. We are studying
how HIV-1 Envelope proteins of varying affinities are sensed by B cells expressing
HIV-1 bnAbs or their germline antigen receptors and initiate early signaling events
for their activation. In the lon
Thomas Norton Denny
Professor in Medicine
Thomas N. Denny, MSc, M.Phil, is the Chief Operating Officer of the Duke Human Vaccine
Institute (DHVI), Associate Dean for Duke Research and Discovery @RTP, and a Professor
of Medicine in the Department of Medicine at Duke University Medical Center. He is
also an Affiliate Member of the Duke Global Health Institute. Previously, he served
on the Health Sector Advisory Council of the Duke University Fuquay School of Business.
Prior to joining Duke, he was an Associate Professor of Pathology, Labo
Feng Gao
Professor Emeritus in Medicine
Dr. Feng Gao is Professor of Medicine at Duke University. The Gao laboratory has a
long-standing interest in elucidating the origins and evolution of human and simian
inmmunodeficiency viruses (HIV and SIV), and in studying HIV/SIV gene function and
pathogenic mechanisms from the evolutionary perspective. These studies have led to
new strategies to better understand HIV origins, biology, pathogenesis and drug resistance,
and to design new AIDS vaccines.
Barton Ford Haynes
Frederic M. Hanes Distinguished Professor of Medicine
Barton F. Haynes, M.D. is the Frederic M. Hanes Professor of Medicine and Immunology,
and Director of the Duke Human Vaccine Institute. Prior to leading the DHVI, Dr. Haynes
served as Chief of the Division of Rheumatology, Allergy and Clinical Immunology,
and later as Chair of the Department of Medicine. As Director of the Duke Human Vaccine
Institute, Bart Haynes is leading a team of investigators working on vaccines for
emerging infections, including tuberculosis, pandemic influenza, emergi
Garnett H. Kelsoe
James B. Duke Distinguished Professor of Immunology
1. Lymphocyte development and antigen-driven diversification of immunoglobulin and
T cell antigen receptor genes. 2. The germinal center reaction and mechanisms for
clonal selection and self - tolerance. The origins of autoimmunity. 3. Interaction
of innate- and adaptive immunity and the role of inflammation in lymphoid organogenesis.
4. The role of secondary V(D)J gene rearrangment in lymphocyte development and malignancies.
5. Mathematical modeling of immune responses,
Hua-Xin Liao
Adjunct Professor in the Department of Medicine
Dr. Liao is a Professor of Medicine and Research Director of Duke Human Vaccine Institute.
Dr. Liao is a MD virologistt rained in China. In early 1980’s, Dr. Liao made
major contributions to the first isolation of epidemic hemorrhagic fever virus (hataanvirus)
from Apodemus agraius using tissue culture in China. The successful identification
and isolation of Hataanvirus enabled the early diagnosis and treatment of the disease,
and advancement of HFRS research towards prevention by de
This author no longer has a Scholars@Duke profile, so the information shown here reflects
their Duke status at the time this item was deposited.
David Charles Montefiori
Professor in Surgery
Dr. Montefiori is Professor and Director of the Laboratory for HIV and COVID-19 Vaccine
Research & Development in the Department of Surgery, Division of Surgical Sciences
at Duke University Medical Center. His major research interests are viral immunology
and HIV and COVID-19 vaccine development, with a special emphasis on neutralizing
antibodies. Multiple aspects of HIV-1 neutralizing antibodies are studied in his laboratory,
including mechanisms of neutralization and escape,
Michael Anthony Moody
Professor of Pediatrics
Tony Moody, MD is a Professor in the Department of Pediatrics, Division of Infectious
Diseases and Professor in the Department of Integrative Immunobiology at Duke University
Medical Center. Research in the Moody lab is focused on understanding the B cell responses
during infection, vaccination, and disease. The lab has become a resource for human
phenotyping, flow characterization, staining and analysis at the Duke Human Vaccine
Institute (DHVI). The Moody lab is currently funded to study in
Georgia Doris Tomaras
Professor in Surgery
Dr. Georgia Tomaras is a tenured Professor of Surgery, Professor of Immunology, Professor
of Molecular Genetics and Microbiology and is a Fellow of the American Academy of
Microbiology (AAM) and a Fellow of the American Association for the Advancement of
Science (AAAS). Dr. Tomaras is Co-Director of the Center for Human Systems Immunology
(CHSI) Duke University and Director of the Duke Center for AIDS Research (CFAR). Her
national and international leadership roles i
Nathan A. Vandergrift
Associate Professor in Medicine
John Franklin Whitesides
Assistant Professor in Medicine
Jae-Sung Yu
Assistant Professor in Medicine
Jae-Sung Yu, PhD is Assistant Professor of Medicine at Duke University Medical Center.
He received his PhD in Microbiology from the University of Connecticut in 1998. Yu
is currently developing rM. smegmatis vectors for HIV-1 vaccines funded by a grant
from the Bill and Melinda Gates grant awarded in July 2006. Yu is also working on
a program project grant, “HIV, TB and Malaria Vaccine Development for Africa,”
expressing HIV and malaria antigens in an attenuated mycobacterium
This author no longer has a Scholars@Duke profile, so the information shown here reflects
their Duke status at the time this item was deposited.
Alphabetical list of authors with Scholars@Duke profiles.
Articles written by Duke faculty are made available through the campus open access policy. For more information see: Duke Open Access Policy
Rights for Collection: Scholarly Articles
Works are deposited here by their authors, and represent their research and opinions, not that of Duke University. Some materials and descriptions may include offensive content. More info