Impact of pre-adapted HIV transmission
Human leukocyte antigen class I (HLA)-restricted CD8(+) T lymphocyte (CTL) responses are crucial to HIV-1 control. Although HIV can evade these responses, the longer-term impact of viral escape mutants remains unclear, as these variants can also reduce intrinsic viral fitness. To address this, we he...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
Nature Publishing Group
2016
|
| _version_ | 1797103703940923392 |
|---|---|
| author | Carlson, J Du, V Pfeifer, N Bansal, A Tan, V Power, K Brumme, C Kreimer, A DeZiel, C Fusi, N Schaefer, M Brockman, M Gilmour, J Price, M Kilembe, W Haubrich, R John, M Mallal, S Shapiro, R Frater, J Harrigan, P Ndung'u, T Allen, S Heckerman, D Sidney, J Allen, T Goulder, P Brumme, Z Hunter, E Goepfert, P |
| author_facet | Carlson, J Du, V Pfeifer, N Bansal, A Tan, V Power, K Brumme, C Kreimer, A DeZiel, C Fusi, N Schaefer, M Brockman, M Gilmour, J Price, M Kilembe, W Haubrich, R John, M Mallal, S Shapiro, R Frater, J Harrigan, P Ndung'u, T Allen, S Heckerman, D Sidney, J Allen, T Goulder, P Brumme, Z Hunter, E Goepfert, P |
| author_sort | Carlson, J |
| collection | OXFORD |
| description | Human leukocyte antigen class I (HLA)-restricted CD8(+) T lymphocyte (CTL) responses are crucial to HIV-1 control. Although HIV can evade these responses, the longer-term impact of viral escape mutants remains unclear, as these variants can also reduce intrinsic viral fitness. To address this, we here developed a metric to determine the degree of HIV adaptation to an HLA profile. We demonstrate that transmission of viruses that are pre-adapted to the HLA molecules expressed in the recipient is associated with impaired immunogenicity, elevated viral load and accelerated CD4(+) T cell decline. Furthermore, the extent of pre-adaptation among circulating viruses explains much of the variation in outcomes attributed to the expression of certain HLA alleles. Thus, viral pre-adaptation exploits 'holes' in the immune response. Accounting for these holes may be key for vaccine strategies seeking to elicit functional responses from viral variants, and to HIV cure strategies that require broad CTL responses to achieve successful eradication of HIV reservoirs. |
| first_indexed | 2024-03-07T06:23:53Z |
| format | Journal article |
| id | oxford-uuid:f39ba95a-f90e-4f35-a35c-11eb4d7cedae |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:23:53Z |
| publishDate | 2016 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:f39ba95a-f90e-4f35-a35c-11eb4d7cedae2022-03-27T12:13:30ZImpact of pre-adapted HIV transmissionJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f39ba95a-f90e-4f35-a35c-11eb4d7cedaeEnglishSymplectic Elements at OxfordNature Publishing Group2016Carlson, JDu, VPfeifer, NBansal, ATan, VPower, KBrumme, CKreimer, ADeZiel, CFusi, NSchaefer, MBrockman, MGilmour, JPrice, MKilembe, WHaubrich, RJohn, MMallal, SShapiro, RFrater, JHarrigan, PNdung'u, TAllen, SHeckerman, DSidney, JAllen, TGoulder, PBrumme, ZHunter, EGoepfert, PHuman leukocyte antigen class I (HLA)-restricted CD8(+) T lymphocyte (CTL) responses are crucial to HIV-1 control. Although HIV can evade these responses, the longer-term impact of viral escape mutants remains unclear, as these variants can also reduce intrinsic viral fitness. To address this, we here developed a metric to determine the degree of HIV adaptation to an HLA profile. We demonstrate that transmission of viruses that are pre-adapted to the HLA molecules expressed in the recipient is associated with impaired immunogenicity, elevated viral load and accelerated CD4(+) T cell decline. Furthermore, the extent of pre-adaptation among circulating viruses explains much of the variation in outcomes attributed to the expression of certain HLA alleles. Thus, viral pre-adaptation exploits 'holes' in the immune response. Accounting for these holes may be key for vaccine strategies seeking to elicit functional responses from viral variants, and to HIV cure strategies that require broad CTL responses to achieve successful eradication of HIV reservoirs. |
| spellingShingle | Carlson, J Du, V Pfeifer, N Bansal, A Tan, V Power, K Brumme, C Kreimer, A DeZiel, C Fusi, N Schaefer, M Brockman, M Gilmour, J Price, M Kilembe, W Haubrich, R John, M Mallal, S Shapiro, R Frater, J Harrigan, P Ndung'u, T Allen, S Heckerman, D Sidney, J Allen, T Goulder, P Brumme, Z Hunter, E Goepfert, P Impact of pre-adapted HIV transmission |
| title | Impact of pre-adapted HIV transmission |
| title_full | Impact of pre-adapted HIV transmission |
| title_fullStr | Impact of pre-adapted HIV transmission |
| title_full_unstemmed | Impact of pre-adapted HIV transmission |
| title_short | Impact of pre-adapted HIV transmission |
| title_sort | impact of pre adapted hiv transmission |
| work_keys_str_mv | AT carlsonj impactofpreadaptedhivtransmission AT duv impactofpreadaptedhivtransmission AT pfeifern impactofpreadaptedhivtransmission AT bansala impactofpreadaptedhivtransmission AT tanv impactofpreadaptedhivtransmission AT powerk impactofpreadaptedhivtransmission AT brummec impactofpreadaptedhivtransmission AT kreimera impactofpreadaptedhivtransmission AT dezielc impactofpreadaptedhivtransmission AT fusin impactofpreadaptedhivtransmission AT schaeferm impactofpreadaptedhivtransmission AT brockmanm impactofpreadaptedhivtransmission AT gilmourj impactofpreadaptedhivtransmission AT pricem impactofpreadaptedhivtransmission AT kilembew impactofpreadaptedhivtransmission AT haubrichr impactofpreadaptedhivtransmission AT johnm impactofpreadaptedhivtransmission AT mallals impactofpreadaptedhivtransmission AT shapiror impactofpreadaptedhivtransmission AT fraterj impactofpreadaptedhivtransmission AT harriganp impactofpreadaptedhivtransmission AT ndungut impactofpreadaptedhivtransmission AT allens impactofpreadaptedhivtransmission AT heckermand impactofpreadaptedhivtransmission AT sidneyj impactofpreadaptedhivtransmission AT allent impactofpreadaptedhivtransmission AT goulderp impactofpreadaptedhivtransmission AT brummez impactofpreadaptedhivtransmission AT huntere impactofpreadaptedhivtransmission AT goepfertp impactofpreadaptedhivtransmission |