The aim of this study is to evaluate the amino acid variability of HIV-1 Gp41, C2-V3, and Nef in a group of patients characterized by different disease progression rates. HIV-1 sequences were collected from 19 Long term non progressor patients (LTNPs), 9 slow progressors (SPs), and 11 rapid progressors (RPs). Phylogenetic trees were estimated by MEGA 6. Differences in amino acid variability among sequences belonging to the 3 groups have been evaluated by amino acid divergence, Shannon entropy analysis, and the number of amino acid mutations (defined as amino acid variations compared with HxB2). The involvement of amino acid mutations on epitope rich regions was also investigated. The population was mainly composed of males (74.3%) and HIV-1 subtype B strains (B: 92.32%, CRF_12BF, A1, C: 2.56% each). Viral load (log10 copies/mL) and CD4+T cell count (cells/mm3) were 3.9 (3.5-4.2) and 618 (504-857) in LTNPs, 3.3 (2.8-4.7) and 463 (333-627) in SPs, and 4.6 (4.3-5.3) and 201 (110-254) in RPs. Gp41 and C2-V3 amino acid divergence was lower in LTNP and SP strains compared to RPs (median value: 0.085 and 0.091 vs. 0.114, p = 0.005 and 0.042) and a trend of lower variability was observed for Nef (p = 0.198). A lower entropy value was observed at 10, 3, and 7 positions of Gp41, C2-V3, and Nef belonging to LTNPs and at 7, 3, and 1 positions of Gp41, C2-V3, and Nef belonging to SPs compared with RPs (p < 0.05). Focusing on epitope rich regions, again a higher degree of conservation was observed in Gp41 and C2-V3 sequences belonging to LTNPs and SPs compared to those belonging to RPs. This study shows that the extent of amino acid variability correlates with a different HIV-1 progression rate. This variability also involves CTL epitope rich regions, thus suggesting its involvement in the immune escape process modulation.

Scutari, R., Faieta, M., D'Arrigo, R., Fabeni, L., Mussini, C., Cossarizza, A., et al. (2018). The degree of HIV-1 amino acid variability is strictly related to different disease progression rates. VIRUS GENES, 54(4), 493-501 [10.1007/s11262-018-1571-2].

The degree of HIV-1 amino acid variability is strictly related to different disease progression rates

Scutari R.;Faieta M.;Perno C. F.;Svicher V.;Aquaro S.
2018-01-01

Abstract

The aim of this study is to evaluate the amino acid variability of HIV-1 Gp41, C2-V3, and Nef in a group of patients characterized by different disease progression rates. HIV-1 sequences were collected from 19 Long term non progressor patients (LTNPs), 9 slow progressors (SPs), and 11 rapid progressors (RPs). Phylogenetic trees were estimated by MEGA 6. Differences in amino acid variability among sequences belonging to the 3 groups have been evaluated by amino acid divergence, Shannon entropy analysis, and the number of amino acid mutations (defined as amino acid variations compared with HxB2). The involvement of amino acid mutations on epitope rich regions was also investigated. The population was mainly composed of males (74.3%) and HIV-1 subtype B strains (B: 92.32%, CRF_12BF, A1, C: 2.56% each). Viral load (log10 copies/mL) and CD4+T cell count (cells/mm3) were 3.9 (3.5-4.2) and 618 (504-857) in LTNPs, 3.3 (2.8-4.7) and 463 (333-627) in SPs, and 4.6 (4.3-5.3) and 201 (110-254) in RPs. Gp41 and C2-V3 amino acid divergence was lower in LTNP and SP strains compared to RPs (median value: 0.085 and 0.091 vs. 0.114, p = 0.005 and 0.042) and a trend of lower variability was observed for Nef (p = 0.198). A lower entropy value was observed at 10, 3, and 7 positions of Gp41, C2-V3, and Nef belonging to LTNPs and at 7, 3, and 1 positions of Gp41, C2-V3, and Nef belonging to SPs compared with RPs (p < 0.05). Focusing on epitope rich regions, again a higher degree of conservation was observed in Gp41 and C2-V3 sequences belonging to LTNPs and SPs compared to those belonging to RPs. This study shows that the extent of amino acid variability correlates with a different HIV-1 progression rate. This variability also involves CTL epitope rich regions, thus suggesting its involvement in the immune escape process modulation.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/07 - Microbiologia e Microbiologia Clinica
English
CTL epitopes; Disease progression; HIV-1; HIV-1 amino acid Shannon entropy; HIV-1 mutation rate; HIV-1 variability; Adult; CD4 Lymphocyte Count; Disease Progression; Epitopes, T-Lymphocyte; Female; Genotype; HIV Envelope Protein gp41; HIV Infections; HIV-1; Humans; Male; Middle Aged; Peptides; Phylogeny; RNA, Viral; Retrospective Studies; T-Lymphocytes, Cytotoxic; Viral Load; Amino Acid Substitution; Mutation
Scutari, R., Faieta, M., D'Arrigo, R., Fabeni, L., Mussini, C., Cossarizza, A., et al. (2018). The degree of HIV-1 amino acid variability is strictly related to different disease progression rates. VIRUS GENES, 54(4), 493-501 [10.1007/s11262-018-1571-2].
Scutari, R; Faieta, M; D'Arrigo, R; Fabeni, L; Mussini, C; Cossarizza, A; Casoli, C; Perno, Cf; Svicher, V; Alteri, C; Aquaro, S
Articolo su rivista
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/210460
Citazioni
  • ???jsp.display-item.citation.pmc??? 1
  • Scopus 2
  • ???jsp.display-item.citation.isi??? 3
social impact