Evidence of Divergent Amino Acid Usage in Comparative Analyses of R5- and X4-Associated HIV-1 Vpr SequencesReportar como inadecuado




Evidence of Divergent Amino Acid Usage in Comparative Analyses of R5- and X4-Associated HIV-1 Vpr Sequences - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

International Journal of Genomics - Volume 2017 2017, Article ID 4081585, 11 pages - https:-doi.org-10.1155-2017-4081585

Research Article

Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USA

Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, USA

School of Biomedical Engineering, Science, and Health Systems, Drexel University, Philadelphia, PA, USA

Center for Clinical and Translational Medicine, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, USA

Division of Infectious Diseases and HIV Medicine, Department of Medicine, Drexel University College of Medicine, Philadelphia, PA, USA

Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA

Correspondence should be addressed to Fred C. Krebs

Received 10 November 2016; Accepted 20 March 2017; Published 23 May 2017

Academic Editor: Margarita Hadzopoulou-Cladaras

Copyright © 2017 Gregory C. Antell et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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.





Autor: Gregory C. Antell, Will Dampier, Benjamas Aiamkitsumrit, Michael R. Nonnemacher, Vanessa Pirrone, Wen Zhong, Katherine Kerch

Fuente: https://www.hindawi.com/



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