REV Responsive Element Polymorphism from Gp41 of Human Immunodeficience Virus Type 1 and Antiretroviral Susceptibility Impact in Patients from Northeast BrazilMelissa Medeiros1*, Erico Arruda1, Christopher Brown2, Jamily Maciel1, Marie-Louise Hammarskjold2, David Rekosh2 and Aldo Lima1
- Corresponding Author:
- Melissa Medeiros
INCT/Department of Fisiology and Phamacology, Faculty of Medicine
Federal University of Ceara, Brazil
Tel: 55-85- 3091-9855
E-mail: [email protected]
Received date: March 19, 2013; Accepted date: April 15, 2013; Published date: April 17, 2013
Citation: Medeiros M, Arruda E, Brown C, Maciel J, Hammarskjold ML, et al. (2013) REV Responsive Element Polymorphism from Gp41 of Human Immunodeficience Virus Type 1 and Antiretroviral Susceptibility Impact in Patients from Northeast Brazil. Mol Biol 2: 110. doi:10.4172/2168-9547.1000110
Copyright: © 2013 Medeiros M, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Introduction: Rev Responsive Element (RRE) is a RNA molecule responsible to mRNA from HIV-1 virus nuclear transportation to cytoplasm through RRE-Rev pathway, essencial to virus replication. Enfuvirtide resistance mutations are primary located in a perimeter of 10 amino acids of HR1, a corresponded region of RRE. Charactherize RRE should provide a new approach for HIV therapy.
Objectives: Sequence and characterize RRE from gp41 to evaluate variability and correlate with laboratory parameters in sequences from HIV-1-infected patients, whitch were receiving regimens including Enfuvirtide, naïve or rescue therapy.
Methods: Sixty-two samples from HIV patients in Northeast Brazil were collected and Thirty-five RRE sequences and clinical follow-up were analyzed, distributed into three groups: N (naïve therapy), T (treated patients with rescue regimens) and F (rescue regimens containing Enfuvirtide). Sequences obtained were aligned with Los Alamos HIV sequence database by using the HIV BLAST Search.
Results: A phylogenetic analyses demonstrated higher prevalence of HIV-1 subtypes B (97.2%). An increased immunology response was observed in CD4 count higher on group T (71,5%) compared with F (2,98%). Group N most commum mutations and polymorphisms were Q32L (41.6%), N42S (8.3%), R46K (33.3%), L54M (41.6%); group T: Q32R (8.3%), R46K (25%), L54M (33.3%); and group F: Q32L (18.2%), G36D (9.1%), V38A (9.1%), N42S (27.3%), N42T (9.1%), R46K (27.3%), L54M (45.4%), K77R (54.5%). Three samples demonstrated significant resistance mutations to fusion inhibitors. Analysis of RRE nucleotide primary sites observed mutation 28A in 27.2% and 8.3% on groups F and N respectively, and 27S in 8.3% on group T. There was selective pressure on HR1 region from HIV-1 patients using antiretrovirals, independent of enfuvirtide exposure.
Conclusions: This study defined most prevalent RRE polymorphisms in Northeast Brazil and suggests highly preserved regions primary sites to Rev connection. Observed a low resistance profile to enfuvirtide in failing regimens with this drug. Selective pressure on HR1 region in failed regimens with out fusion inhibidors was detected.