title: Human immunodeficiency virus type 1 gp 41 mutations in proviral DNA among antiretroviral treatment-naive individuals from India.
abstract: The HIV-1 gp41 has been identified as an important target for the immune response, for the development of antiviral and vaccine strategies, and for epidemiologic studies. This study describes the HIV-1 env gp41 region mutations, associated with enfuvirtide (ENF) resistance, in proviral DNA from PBMCs in antiretroviral treatment-naive individuals from Pune, India. Twenty-one antiretroviral drug-naive chronically HIV-1-infected individuals were enrolled. The study sequences belonged to subtype C (n = 17), subtype A1 (n = 2), and CRF_AE (n = 2). In subtype B-infected individuals, the various HR1 region substitutions in env gp41 that have been associated with ENF resistance include A30V, L33S/T/V, L34M, G36D/E/S/V, I37T/K/V, V38A/M/E/G, Q39R, Q40H, N42T/D, N43D/K/S, L44M, L45M, R46M, L54M, and Q56K/R as well as N126K and S138A in the HR2 region. The study sequences did not reveal any ENF resistance-associated mutations at env gp41 amino acid positions: 36 to 45. The presence of L54M and Q56K in combination is associated with 5-fold reduced sensitivity to inhibition by ENF. The mutation L54M was seen in seven subtype C and two CRF_AE study sequences. Q56K was observed in a subtype A1 sequence. All the study sequences harbored N42S, a natural polymorphism associated with increased susceptibility to ENF. Of the mutations V38A and N140I, known to provide immunologic gain, the latter was observed in four subtype C sequences. This is the first study from India highlighting the presence of certain mutations in Indian subtype C env gp41, which may play a role in the evolution of subtype-specific variations in the resistance to ENF and associated immune response.
authors.affiliation: Department of Microbiology, Armed Forces Medical College, Pune, India. sensourav@hotmail.com
authors.forename: Sourav
authors.initials: S
authors.lastname: Sen
authors.forename: S P
authors.initials: SP
authors.lastname: Tripathy
authors.forename: A K
authors.initials: AK
authors.lastname: Sahni
authors.forename: R M
authors.initials: RM
authors.lastname: Gupta
authors.forename: K
authors.initials: K
authors.lastname: Kapila
authors.forename: G S
authors.initials: GS
authors.lastname: Chopra
authors.forename: Vaishali M
authors.initials: VM
authors.lastname: Chimanpure
authors.forename: Ajit A
authors.initials: AA
authors.lastname: Patil
authors.forename: R S
authors.initials: RS
authors.lastname: Paranjape
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D019380:Anti-HIV Agents / Q000494:pharmacology; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D024882:Drug Resistance, Viral; D000077560:Enfuvirtide; D015700:HIV Envelope Protein gp41 / Q000235:genetics* / Q000494:pharmacology; D015497:HIV-1 / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D007194:India; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010446:Peptide Fragments / Q000494:pharmacology; D011533:Proviruses / Q000235:genetics* / Q000302:isolation & purification; D017422:Sequence Analysis, DNA
chemical_list: D019380:Anti-HIV Agents; D004279:DNA, Viral; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; C514787:gp41 protein, Human immunodeficiency virus 1; D000077560:Enfuvirtide