In vivo emergence of HIV-1 highly sensitive to neutralizing antibodies.
<h4>Background</h4>The rapid and continual viral escape from neutralizing antibodies is well documented in HIV-1 infection. Here we report in vivo emergence of viruses with heightened sensitivity to neutralizing antibodies, sometimes paralleling the development of neutralization escape.&...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0023961&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849470485187788800 |
|---|---|
| author | Marlén M I Aasa-Chapman Kelly M Cheney Stéphane Hué Anna Forsman Stephen O'Farrell Pierre Pellegrino Ian Williams Áine McKnight |
| author_facet | Marlén M I Aasa-Chapman Kelly M Cheney Stéphane Hué Anna Forsman Stephen O'Farrell Pierre Pellegrino Ian Williams Áine McKnight |
| author_sort | Marlén M I Aasa-Chapman |
| collection | DOAJ |
| description | <h4>Background</h4>The rapid and continual viral escape from neutralizing antibodies is well documented in HIV-1 infection. Here we report in vivo emergence of viruses with heightened sensitivity to neutralizing antibodies, sometimes paralleling the development of neutralization escape.<h4>Methodology/principal findings</h4>Sequential viral envs were amplified from seven HIV-1 infected men monitored from seroconversion up to 5 years after infection. Env-recombinant infectious molecular clones were generated and tested for coreceptor use, macrophage tropism and neutralization sensitivity to homologous and heterologous serum, soluble CD4 and monoclonal antibodies IgG1b12, 2G12 and 17b. We found that HIV-1 evolves sensitivity to contemporaneous neutralizing antibodies during infection. Neutralization sensitive viruses grow out even when potent autologous neutralizing antibodies are present in patient serum. Increased sensitivity to neutralization was associated with susceptibility of the CD4 binding site or epitopes induced after CD4 binding, and mediated by complex envelope determinants including V3 and V4 residues. The development of neutralization sensitive viruses occurred without clinical progression, coreceptor switch or change in tropism for primary macrophages.<h4>Conclusions</h4>We propose that an interplay of selective forces for greater virus replication efficiency without the need to resist neutralizing antibodies in a compartment protected from immune surveillance may explain the temporal course described here for the in vivo emergence of HIV-1 isolates with high sensitivity to neutralizing antibodies. |
| format | Article |
| id | doaj-art-4559cf88a5df46d596ccac2954b80d1e |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-4559cf88a5df46d596ccac2954b80d1e2025-08-20T03:25:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0168e2396110.1371/journal.pone.0023961In vivo emergence of HIV-1 highly sensitive to neutralizing antibodies.Marlén M I Aasa-ChapmanKelly M CheneyStéphane HuéAnna ForsmanStephen O'FarrellPierre PellegrinoIan WilliamsÁine McKnight<h4>Background</h4>The rapid and continual viral escape from neutralizing antibodies is well documented in HIV-1 infection. Here we report in vivo emergence of viruses with heightened sensitivity to neutralizing antibodies, sometimes paralleling the development of neutralization escape.<h4>Methodology/principal findings</h4>Sequential viral envs were amplified from seven HIV-1 infected men monitored from seroconversion up to 5 years after infection. Env-recombinant infectious molecular clones were generated and tested for coreceptor use, macrophage tropism and neutralization sensitivity to homologous and heterologous serum, soluble CD4 and monoclonal antibodies IgG1b12, 2G12 and 17b. We found that HIV-1 evolves sensitivity to contemporaneous neutralizing antibodies during infection. Neutralization sensitive viruses grow out even when potent autologous neutralizing antibodies are present in patient serum. Increased sensitivity to neutralization was associated with susceptibility of the CD4 binding site or epitopes induced after CD4 binding, and mediated by complex envelope determinants including V3 and V4 residues. The development of neutralization sensitive viruses occurred without clinical progression, coreceptor switch or change in tropism for primary macrophages.<h4>Conclusions</h4>We propose that an interplay of selective forces for greater virus replication efficiency without the need to resist neutralizing antibodies in a compartment protected from immune surveillance may explain the temporal course described here for the in vivo emergence of HIV-1 isolates with high sensitivity to neutralizing antibodies.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0023961&type=printable |
| spellingShingle | Marlén M I Aasa-Chapman Kelly M Cheney Stéphane Hué Anna Forsman Stephen O'Farrell Pierre Pellegrino Ian Williams Áine McKnight In vivo emergence of HIV-1 highly sensitive to neutralizing antibodies. PLoS ONE |
| title | In vivo emergence of HIV-1 highly sensitive to neutralizing antibodies. |
| title_full | In vivo emergence of HIV-1 highly sensitive to neutralizing antibodies. |
| title_fullStr | In vivo emergence of HIV-1 highly sensitive to neutralizing antibodies. |
| title_full_unstemmed | In vivo emergence of HIV-1 highly sensitive to neutralizing antibodies. |
| title_short | In vivo emergence of HIV-1 highly sensitive to neutralizing antibodies. |
| title_sort | in vivo emergence of hiv 1 highly sensitive to neutralizing antibodies |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0023961&type=printable |
| work_keys_str_mv | AT marlenmiaasachapman invivoemergenceofhiv1highlysensitivetoneutralizingantibodies AT kellymcheney invivoemergenceofhiv1highlysensitivetoneutralizingantibodies AT stephanehue invivoemergenceofhiv1highlysensitivetoneutralizingantibodies AT annaforsman invivoemergenceofhiv1highlysensitivetoneutralizingantibodies AT stephenofarrell invivoemergenceofhiv1highlysensitivetoneutralizingantibodies AT pierrepellegrino invivoemergenceofhiv1highlysensitivetoneutralizingantibodies AT ianwilliams invivoemergenceofhiv1highlysensitivetoneutralizingantibodies AT ainemcknight invivoemergenceofhiv1highlysensitivetoneutralizingantibodies |