Evidence of Divergent Amino Acid Usage in Comparative Analyses of R5- and X4-Associated HIV-1 Vpr Sequences
Vpr is an HIV-1 accessory protein that plays numerous roles during viral replication, and some of which are cell type dependent. To test the hypothesis that HIV-1 tropism extends beyond the envelope into the vpr gene, studies were performed to identify the associations between coreceptor usage and V...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2017-01-01
|
| Series: | International Journal of Genomics |
| Online Access: | http://dx.doi.org/10.1155/2017/4081585 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832560342504308736 |
|---|---|
| author | Gregory C. Antell Will Dampier Benjamas Aiamkitsumrit Michael R. Nonnemacher Vanessa Pirrone Wen Zhong Katherine Kercher Shendra Passic Jean Williams Yucheng Liu Tony James Jeffrey M. Jacobson Zsofia Szep Brian Wigdahl Fred C. Krebs |
| author_facet | Gregory C. Antell Will Dampier Benjamas Aiamkitsumrit Michael R. Nonnemacher Vanessa Pirrone Wen Zhong Katherine Kercher Shendra Passic Jean Williams Yucheng Liu Tony James Jeffrey M. Jacobson Zsofia Szep Brian Wigdahl Fred C. Krebs |
| author_sort | Gregory C. Antell |
| collection | DOAJ |
| description | Vpr is an HIV-1 accessory protein that plays numerous roles during viral replication, and some of which are cell type dependent. To test the hypothesis that HIV-1 tropism extends beyond the envelope into the vpr gene, studies were performed to identify the associations between coreceptor usage and Vpr variation in HIV-1-infected patients. Colinear HIV-1 Env-V3 and Vpr amino acid sequences were obtained from the LANL HIV-1 sequence database and from well-suppressed patients in the Drexel/Temple Medicine CNS AIDS Research and Eradication Study (CARES) Cohort. Genotypic classification of Env-V3 sequences as X4 (CXCR4-utilizing) or R5 (CCR5-utilizing) was used to group colinear Vpr sequences. To reveal the sequences associated with a specific coreceptor usage genotype, Vpr amino acid sequences were assessed for amino acid diversity and Jensen-Shannon divergence between the two groups. Five amino acid alphabets were used to comprehensively examine the impact of amino acid substitutions involving side chains with similar physiochemical properties. Positions 36, 37, 41, 89, and 96 of Vpr were characterized by statistically significant divergence across multiple alphabets when X4 and R5 sequence groups were compared. In addition, consensus amino acid switches were found at positions 37 and 41 in comparisons of the R5 and X4 sequence populations. These results suggest an evolutionary link between Vpr and gp120 in HIV-1-infected patients. |
| format | Article |
| id | doaj-art-bbe681d11e4c404fab6a15ed80c1bd19 |
| institution | Kabale University |
| issn | 2314-436X 2314-4378 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Genomics |
| spelling | doaj-art-bbe681d11e4c404fab6a15ed80c1bd192025-02-03T01:27:48ZengWileyInternational Journal of Genomics2314-436X2314-43782017-01-01201710.1155/2017/40815854081585Evidence of Divergent Amino Acid Usage in Comparative Analyses of R5- and X4-Associated HIV-1 Vpr SequencesGregory C. Antell0Will Dampier1Benjamas Aiamkitsumrit2Michael R. Nonnemacher3Vanessa Pirrone4Wen Zhong5Katherine Kercher6Shendra Passic7Jean Williams8Yucheng Liu9Tony James10Jeffrey M. Jacobson11Zsofia Szep12Brian Wigdahl13Fred C. Krebs14Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USADepartment of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USADepartment of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USADepartment of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USADepartment of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USADepartment of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USADepartment of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USADepartment of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USADepartment of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USADepartment of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USADepartment of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USACenter for Clinical and Translational Medicine, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, USACenter for Clinical and Translational Medicine, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, USADepartment of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USADepartment of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USAVpr is an HIV-1 accessory protein that plays numerous roles during viral replication, and some of which are cell type dependent. To test the hypothesis that HIV-1 tropism extends beyond the envelope into the vpr gene, studies were performed to identify the associations between coreceptor usage and Vpr variation in HIV-1-infected patients. Colinear HIV-1 Env-V3 and Vpr amino acid sequences were obtained from the LANL HIV-1 sequence database and from well-suppressed patients in the Drexel/Temple Medicine CNS AIDS Research and Eradication Study (CARES) Cohort. Genotypic classification of Env-V3 sequences as X4 (CXCR4-utilizing) or R5 (CCR5-utilizing) was used to group colinear Vpr sequences. To reveal the sequences associated with a specific coreceptor usage genotype, Vpr amino acid sequences were assessed for amino acid diversity and Jensen-Shannon divergence between the two groups. Five amino acid alphabets were used to comprehensively examine the impact of amino acid substitutions involving side chains with similar physiochemical properties. Positions 36, 37, 41, 89, and 96 of Vpr were characterized by statistically significant divergence across multiple alphabets when X4 and R5 sequence groups were compared. In addition, consensus amino acid switches were found at positions 37 and 41 in comparisons of the R5 and X4 sequence populations. These results suggest an evolutionary link between Vpr and gp120 in HIV-1-infected patients.http://dx.doi.org/10.1155/2017/4081585 |
| spellingShingle | Gregory C. Antell Will Dampier Benjamas Aiamkitsumrit Michael R. Nonnemacher Vanessa Pirrone Wen Zhong Katherine Kercher Shendra Passic Jean Williams Yucheng Liu Tony James Jeffrey M. Jacobson Zsofia Szep Brian Wigdahl Fred C. Krebs Evidence of Divergent Amino Acid Usage in Comparative Analyses of R5- and X4-Associated HIV-1 Vpr Sequences International Journal of Genomics |
| title | Evidence of Divergent Amino Acid Usage in Comparative Analyses of R5- and X4-Associated HIV-1 Vpr Sequences |
| title_full | Evidence of Divergent Amino Acid Usage in Comparative Analyses of R5- and X4-Associated HIV-1 Vpr Sequences |
| title_fullStr | Evidence of Divergent Amino Acid Usage in Comparative Analyses of R5- and X4-Associated HIV-1 Vpr Sequences |
| title_full_unstemmed | Evidence of Divergent Amino Acid Usage in Comparative Analyses of R5- and X4-Associated HIV-1 Vpr Sequences |
| title_short | Evidence of Divergent Amino Acid Usage in Comparative Analyses of R5- and X4-Associated HIV-1 Vpr Sequences |
| title_sort | evidence of divergent amino acid usage in comparative analyses of r5 and x4 associated hiv 1 vpr sequences |
| url | http://dx.doi.org/10.1155/2017/4081585 |
| work_keys_str_mv | AT gregorycantell evidenceofdivergentaminoacidusageincomparativeanalysesofr5andx4associatedhiv1vprsequences AT willdampier evidenceofdivergentaminoacidusageincomparativeanalysesofr5andx4associatedhiv1vprsequences AT benjamasaiamkitsumrit evidenceofdivergentaminoacidusageincomparativeanalysesofr5andx4associatedhiv1vprsequences AT michaelrnonnemacher evidenceofdivergentaminoacidusageincomparativeanalysesofr5andx4associatedhiv1vprsequences AT vanessapirrone evidenceofdivergentaminoacidusageincomparativeanalysesofr5andx4associatedhiv1vprsequences AT wenzhong evidenceofdivergentaminoacidusageincomparativeanalysesofr5andx4associatedhiv1vprsequences AT katherinekercher evidenceofdivergentaminoacidusageincomparativeanalysesofr5andx4associatedhiv1vprsequences AT shendrapassic evidenceofdivergentaminoacidusageincomparativeanalysesofr5andx4associatedhiv1vprsequences AT jeanwilliams evidenceofdivergentaminoacidusageincomparativeanalysesofr5andx4associatedhiv1vprsequences AT yuchengliu evidenceofdivergentaminoacidusageincomparativeanalysesofr5andx4associatedhiv1vprsequences AT tonyjames evidenceofdivergentaminoacidusageincomparativeanalysesofr5andx4associatedhiv1vprsequences AT jeffreymjacobson evidenceofdivergentaminoacidusageincomparativeanalysesofr5andx4associatedhiv1vprsequences AT zsofiaszep evidenceofdivergentaminoacidusageincomparativeanalysesofr5andx4associatedhiv1vprsequences AT brianwigdahl evidenceofdivergentaminoacidusageincomparativeanalysesofr5andx4associatedhiv1vprsequences AT fredckrebs evidenceofdivergentaminoacidusageincomparativeanalysesofr5andx4associatedhiv1vprsequences |