A single point mutation in HIV-1 V3 loop alters the immunogenic properties of rgp120

A single point mutation in HIV-1 V3 loop alters the immunogenic properties of rgp120 The results of the study presented in this report show that clones of env derived from genetically divergent HIV-1 field isolates fall into two major subsets based on the predicted secondary structure of the V3 region in gp120. One subset exemplified by the clones A-UG06c, B-RT3.12 and C-UG045 is predicted to assume a β-turn conformation in the V3 loop and comprises the GPG residues. The other subset exemplified by the clones D-UG23c and D-UG042 (G ) are deficient in the expression of the β-turn in the loop. Since secondary conformations are highly likely to confer antigenic properties in a protein backbone at least for B cells, we have used nucleic acid immunization to test the effect of the β-turn deficiency on the immunogenic potential of rgp120 encoded in these field isolates. As hypothesized, inoculation of BALB/c mice with the env plasmid encoding the β-turn expressing rgp120 molecules resulted in the development of a vigorous antibody response to the homologous V3 loop peptides. In contrast, immunization with an rgp120 clone deficient in the β-turn in the V3 loop showed no evidence of antibody development to the V3 loop. Instead, the latter clones triggered T cell proliferative responses and markedly increased the level of IL-2 and IFN-γ production by T cells. Significantly, reconstitution of the β-turn conformation by site-directed mutagenesis of a single V3 loop residue yielded rgp120 molecules which restored antibody production while diminishing the cell-mediated immune (CMI) responses to the V3 residue. These observations demonstrate the marked impact of a single amino acid substitution on the immunogenic properties of V3 region in gp120 encoded by divergent HIV-1 field isolates. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Virology Springer Journals

A single point mutation in HIV-1 V3 loop alters the immunogenic properties of rgp120

Loading next page...
 
/lp/springer_journal/a-single-point-mutation-in-hiv-1-v3-loop-alters-the-immunogenic-ThSqAmsLPH
Publisher
Springer-Verlag
Copyright
Copyright © 2000 by Springer-Verlag/Wien
Subject
Legacy
ISSN
0304-8608
eISSN
1432-8798
D.O.I.
10.1007/s007050070041
Publisher site
See Article on Publisher Site

Abstract

The results of the study presented in this report show that clones of env derived from genetically divergent HIV-1 field isolates fall into two major subsets based on the predicted secondary structure of the V3 region in gp120. One subset exemplified by the clones A-UG06c, B-RT3.12 and C-UG045 is predicted to assume a β-turn conformation in the V3 loop and comprises the GPG residues. The other subset exemplified by the clones D-UG23c and D-UG042 (G ) are deficient in the expression of the β-turn in the loop. Since secondary conformations are highly likely to confer antigenic properties in a protein backbone at least for B cells, we have used nucleic acid immunization to test the effect of the β-turn deficiency on the immunogenic potential of rgp120 encoded in these field isolates. As hypothesized, inoculation of BALB/c mice with the env plasmid encoding the β-turn expressing rgp120 molecules resulted in the development of a vigorous antibody response to the homologous V3 loop peptides. In contrast, immunization with an rgp120 clone deficient in the β-turn in the V3 loop showed no evidence of antibody development to the V3 loop. Instead, the latter clones triggered T cell proliferative responses and markedly increased the level of IL-2 and IFN-γ production by T cells. Significantly, reconstitution of the β-turn conformation by site-directed mutagenesis of a single V3 loop residue yielded rgp120 molecules which restored antibody production while diminishing the cell-mediated immune (CMI) responses to the V3 residue. These observations demonstrate the marked impact of a single amino acid substitution on the immunogenic properties of V3 region in gp120 encoded by divergent HIV-1 field isolates.

Journal

Archives of VirologySpringer Journals

Published: Oct 1, 2000

There are no references for this article.

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 12 million articles from more than
10,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Unlimited reading

Read as many articles as you need. Full articles with original layout, charts and figures. Read online, from anywhere.

Stay up to date

Keep up with your field with Personalized Recommendations and Follow Journals to get automatic updates.

Organize your research

It’s easy to organize your research with our built-in tools.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve Freelancer

DeepDyve Pro

Price
FREE
$49/month

$360/year
Save searches from Google Scholar, PubMed
Create lists to organize your research
Export lists, citations
Access to DeepDyve database
Abstract access only
Unlimited access to over
18 million full-text articles
Print
20 pages/month
PDF Discount
20% off