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Study of the HIV-2 Env cytoplasmic tail variability and its impact on Tat, Rev and Nef.

Bakouche N, Vandenbroucke AT, Goubau P, Ruelle J - PLoS ONE (2013)

Bottom Line: A 70% reduction of the length of the CT region affected the HIV-2 ROD and EHO strains in vitro due to a premature stop codon in the env gene.These regions don't affect the rev and Nef amino acids composition which evolves independently.In contrast, Tat co-evolves with the Env CT.

View Article: PubMed Central - PubMed

Affiliation: Institut de recherche expérimentale et clinique, Université catholique de Louvain, Brussels, Belgium.

ABSTRACT

Background: The HIV-2 env's 3' end encodes the cytoplasmic tail (CT) of the Env protein. This genomic region also encodes the rev, Tat and Nef protein in overlapping reading frames. We studied the variability in the CT coding region in 46 clinical specimens and in 2 reference strains by sequencing and by culturing. The aims were to analyse the variability of Env CT and the evolution of proteins expressed from overlapping coding sequences.

Results: A 70% reduction of the length of the CT region affected the HIV-2 ROD and EHO strains in vitro due to a premature stop codon in the env gene. In clinical samples this wasn't observed, but the CT length varied due to insertions and deletions. We noted 3 conserved and 3 variable regions in the CT. The conserved regions were those containing residues involved in Env endocytosis, the potential HIV-2 CT region implicated in the NF-kB activation and the potential end of the lentiviral lytic peptide one. The variable regions were the potential HIV-2 Kennedy region, the potential lentiviral lytic peptide two and the beginning of the potential lentiviral lytic peptide one. A very hydrophobic region was coded downstream of the premature stop codon observed in vitro, suggesting a membrane spanning region. Interestingly, the nucleotides that are responsible for the variability of the CT don't impact rev and Nef. However, in the Kennedy-like coding region variability resulted only from nucleotide changes that impacted Env and Tat together.

Conclusion: The HIV-2 Env, Tat and Rev C-terminal part are subject to major length variations in both clinical samples and cultured strains. The HIV-2 Env CT contains variable and conserved regions. These regions don't affect the rev and Nef amino acids composition which evolves independently. In contrast, Tat co-evolves with the Env CT.

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Related in: MedlinePlus

Alignment of 27 virus/provirus CT HIV-2 aa sequences (1 sequence per patient), classified by similarity.The GenBank accession number is followed by the HIV-2 group (A or B). To construct the alignment, only the most recent sample was included. The conserved aa are highlighted in red (>85% of conservation). In green appears the most represented aa for each position (>50% of conservation). Blue corresponds to variable positions with similar aa.
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pone-0079129-g001: Alignment of 27 virus/provirus CT HIV-2 aa sequences (1 sequence per patient), classified by similarity.The GenBank accession number is followed by the HIV-2 group (A or B). To construct the alignment, only the most recent sample was included. The conserved aa are highlighted in red (>85% of conservation). In green appears the most represented aa for each position (>50% of conservation). Blue corresponds to variable positions with similar aa.

Mentions: For each patient we show: accession number of the sequences identical to Figure 1, viral load, CD4 count, presence of AIDS (Yes=Y, No=N), antiretroviral (ARV) treatment before sampling, gender (Male=M, Female= F) and age at sampling. N.A.= Not available.


Study of the HIV-2 Env cytoplasmic tail variability and its impact on Tat, Rev and Nef.

Bakouche N, Vandenbroucke AT, Goubau P, Ruelle J - PLoS ONE (2013)

Alignment of 27 virus/provirus CT HIV-2 aa sequences (1 sequence per patient), classified by similarity.The GenBank accession number is followed by the HIV-2 group (A or B). To construct the alignment, only the most recent sample was included. The conserved aa are highlighted in red (>85% of conservation). In green appears the most represented aa for each position (>50% of conservation). Blue corresponds to variable positions with similar aa.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3815105&req=5

pone-0079129-g001: Alignment of 27 virus/provirus CT HIV-2 aa sequences (1 sequence per patient), classified by similarity.The GenBank accession number is followed by the HIV-2 group (A or B). To construct the alignment, only the most recent sample was included. The conserved aa are highlighted in red (>85% of conservation). In green appears the most represented aa for each position (>50% of conservation). Blue corresponds to variable positions with similar aa.
Mentions: For each patient we show: accession number of the sequences identical to Figure 1, viral load, CD4 count, presence of AIDS (Yes=Y, No=N), antiretroviral (ARV) treatment before sampling, gender (Male=M, Female= F) and age at sampling. N.A.= Not available.

Bottom Line: A 70% reduction of the length of the CT region affected the HIV-2 ROD and EHO strains in vitro due to a premature stop codon in the env gene.These regions don't affect the rev and Nef amino acids composition which evolves independently.In contrast, Tat co-evolves with the Env CT.

View Article: PubMed Central - PubMed

Affiliation: Institut de recherche expérimentale et clinique, Université catholique de Louvain, Brussels, Belgium.

ABSTRACT

Background: The HIV-2 env's 3' end encodes the cytoplasmic tail (CT) of the Env protein. This genomic region also encodes the rev, Tat and Nef protein in overlapping reading frames. We studied the variability in the CT coding region in 46 clinical specimens and in 2 reference strains by sequencing and by culturing. The aims were to analyse the variability of Env CT and the evolution of proteins expressed from overlapping coding sequences.

Results: A 70% reduction of the length of the CT region affected the HIV-2 ROD and EHO strains in vitro due to a premature stop codon in the env gene. In clinical samples this wasn't observed, but the CT length varied due to insertions and deletions. We noted 3 conserved and 3 variable regions in the CT. The conserved regions were those containing residues involved in Env endocytosis, the potential HIV-2 CT region implicated in the NF-kB activation and the potential end of the lentiviral lytic peptide one. The variable regions were the potential HIV-2 Kennedy region, the potential lentiviral lytic peptide two and the beginning of the potential lentiviral lytic peptide one. A very hydrophobic region was coded downstream of the premature stop codon observed in vitro, suggesting a membrane spanning region. Interestingly, the nucleotides that are responsible for the variability of the CT don't impact rev and Nef. However, in the Kennedy-like coding region variability resulted only from nucleotide changes that impacted Env and Tat together.

Conclusion: The HIV-2 Env, Tat and Rev C-terminal part are subject to major length variations in both clinical samples and cultured strains. The HIV-2 Env CT contains variable and conserved regions. These regions don't affect the rev and Nef amino acids composition which evolves independently. In contrast, Tat co-evolves with the Env CT.

Show MeSH
Related in: MedlinePlus