Cryptic determinant of α4β7 binding in the V2 loop of HIV-1 gp120.
The peptide segment of the second variable loop of HIV-1 spanning positions 166-181 harbors two functionally important sites. The first, spanning positions 179-181, engages the human α4β7 integrin receptor which is involved in T-cell gut-homing and may play a role in human immunodeficiency virus (HI...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4180765?pdf=render |
| _version_ | 1811279320803442688 |
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| author | Boonrat Tassaneetrithep Doreen Tivon James Swetnam Nicos Karasavvas Nelson L Michael Jerome H Kim Mary Marovich Timothy Cardozo |
| author_facet | Boonrat Tassaneetrithep Doreen Tivon James Swetnam Nicos Karasavvas Nelson L Michael Jerome H Kim Mary Marovich Timothy Cardozo |
| author_sort | Boonrat Tassaneetrithep |
| collection | DOAJ |
| description | The peptide segment of the second variable loop of HIV-1 spanning positions 166-181 harbors two functionally important sites. The first, spanning positions 179-181, engages the human α4β7 integrin receptor which is involved in T-cell gut-homing and may play a role in human immunodeficiency virus (HIV)-host cell interactions. The second, at positions 166-178, is a major target of anti-V2 antibodies elicited by the ALVAC/AIDSVAX vaccine used in the RV144 clinical trial. Notably, these two sites are directly adjacent, but do not overlap. Here, we report the identity of a second determinant of α4β7 binding located at positions 170-172 of the V2 loop. This segment - tripeptide QRV170-172- is located within the second site, yet functionally affects the first site. The absence of this segment abrogates α4β7 binding in peptides bearing the same sequence from position 173-185 as the V2 loops of the RV144 vaccines. However, peptides exhibiting V2 loop sequences from heterologous HIV-1 strains that include this QRV170-172 motif bind the α4β7 receptor on cells. Therefore, the peptide segment at positions 166-178 of the V2 loop of HIV-1 viruses appears to harbor a cryptic determinant of α4β7 binding. Prior studies show that the anti-V2 antibody response elicited by the RV144 vaccine, along with immune pressure inferred from a sieve analysis, is directed to this same region of the V2 loop. Accordingly, the anti-V2 antibodies that apparently reduced the risk of infection in the RV144 trial may have functioned by blocking α4β7-mediated HIV-host cell interactions via this cryptic determinant. |
| first_indexed | 2024-04-13T00:52:34Z |
| format | Article |
| id | doaj.art-c9a7733b36254fe790fc088138c73c5f |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T00:52:34Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-c9a7733b36254fe790fc088138c73c5f2022-12-22T03:09:51ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0199e10844610.1371/journal.pone.0108446Cryptic determinant of α4β7 binding in the V2 loop of HIV-1 gp120.Boonrat TassaneetrithepDoreen TivonJames SwetnamNicos KarasavvasNelson L MichaelJerome H KimMary MarovichTimothy CardozoThe peptide segment of the second variable loop of HIV-1 spanning positions 166-181 harbors two functionally important sites. The first, spanning positions 179-181, engages the human α4β7 integrin receptor which is involved in T-cell gut-homing and may play a role in human immunodeficiency virus (HIV)-host cell interactions. The second, at positions 166-178, is a major target of anti-V2 antibodies elicited by the ALVAC/AIDSVAX vaccine used in the RV144 clinical trial. Notably, these two sites are directly adjacent, but do not overlap. Here, we report the identity of a second determinant of α4β7 binding located at positions 170-172 of the V2 loop. This segment - tripeptide QRV170-172- is located within the second site, yet functionally affects the first site. The absence of this segment abrogates α4β7 binding in peptides bearing the same sequence from position 173-185 as the V2 loops of the RV144 vaccines. However, peptides exhibiting V2 loop sequences from heterologous HIV-1 strains that include this QRV170-172 motif bind the α4β7 receptor on cells. Therefore, the peptide segment at positions 166-178 of the V2 loop of HIV-1 viruses appears to harbor a cryptic determinant of α4β7 binding. Prior studies show that the anti-V2 antibody response elicited by the RV144 vaccine, along with immune pressure inferred from a sieve analysis, is directed to this same region of the V2 loop. Accordingly, the anti-V2 antibodies that apparently reduced the risk of infection in the RV144 trial may have functioned by blocking α4β7-mediated HIV-host cell interactions via this cryptic determinant.http://europepmc.org/articles/PMC4180765?pdf=render |
| spellingShingle | Boonrat Tassaneetrithep Doreen Tivon James Swetnam Nicos Karasavvas Nelson L Michael Jerome H Kim Mary Marovich Timothy Cardozo Cryptic determinant of α4β7 binding in the V2 loop of HIV-1 gp120. PLoS ONE |
| title | Cryptic determinant of α4β7 binding in the V2 loop of HIV-1 gp120. |
| title_full | Cryptic determinant of α4β7 binding in the V2 loop of HIV-1 gp120. |
| title_fullStr | Cryptic determinant of α4β7 binding in the V2 loop of HIV-1 gp120. |
| title_full_unstemmed | Cryptic determinant of α4β7 binding in the V2 loop of HIV-1 gp120. |
| title_short | Cryptic determinant of α4β7 binding in the V2 loop of HIV-1 gp120. |
| title_sort | cryptic determinant of α4β7 binding in the v2 loop of hiv 1 gp120 |
| url | http://europepmc.org/articles/PMC4180765?pdf=render |
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