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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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Env CT sequence alignment of the major primate lentiviruses.HIV-1: (Swiss-prot: P04578), SIVcpz: (Swiss-prot: P17281), SIVgor: (GenBank:FJ424865.1), HIV-2: CT consensus sequence from the article, SIVmac: (Swiss-prot: P08810) and SIVsm: (Swiss-prot: P12492). The conserved aa (in red) are aa of the endocytosis signal (region A) and the aa at the end of the LLP-1 region (region G). The aa implicated in SIVmac NF-kB activation (end of region A) are absent in HIV-1 and its lineage (SIVcpz and gor).
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pone-0079129-g002: Env CT sequence alignment of the major primate lentiviruses.HIV-1: (Swiss-prot: P04578), SIVcpz: (Swiss-prot: P17281), SIVgor: (GenBank:FJ424865.1), HIV-2: CT consensus sequence from the article, SIVmac: (Swiss-prot: P08810) and SIVsm: (Swiss-prot: P12492). The conserved aa (in red) are aa of the endocytosis signal (region A) and the aa at the end of the LLP-1 region (region G). The aa implicated in SIVmac NF-kB activation (end of region A) are absent in HIV-1 and its lineage (SIVcpz and gor).

Mentions: We divided the two final regions of our sequences in two arginine rich regions. The first region was a small LLP-3/LLP-1 inter-region (position 126 to 136 consensus RATRETLANAWR; region F, Table 3), and the second was the LLP-1 homologous sequence (position 137 to 165 consensuses GLWGALQRIGRGIL/AVPRRIRQGAELALL; with the final di-leucine motif; region G). The beginning of the LLP-1 region was highly variable (position 137 to 150, aa before the slash; G start, Table 3). This part contained also a lot of positions with mixtures of aa. In contrast, the end of the LLP-1 (aa after the slash) was the most constant part of the CT (G end, Table 3). Interestingly, this LLP-1 region was very rich in arginine and ended in all our sequences with the final di-leucine motif. Furthermore, the LLP-1 conserved part is also conserved among all primate lentiviruses (Figure 2).


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)

Env CT sequence alignment of the major primate lentiviruses.HIV-1: (Swiss-prot: P04578), SIVcpz: (Swiss-prot: P17281), SIVgor: (GenBank:FJ424865.1), HIV-2: CT consensus sequence from the article, SIVmac: (Swiss-prot: P08810) and SIVsm: (Swiss-prot: P12492). The conserved aa (in red) are aa of the endocytosis signal (region A) and the aa at the end of the LLP-1 region (region G). The aa implicated in SIVmac NF-kB activation (end of region A) are absent in HIV-1 and its lineage (SIVcpz and gor).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3815105&req=5

pone-0079129-g002: Env CT sequence alignment of the major primate lentiviruses.HIV-1: (Swiss-prot: P04578), SIVcpz: (Swiss-prot: P17281), SIVgor: (GenBank:FJ424865.1), HIV-2: CT consensus sequence from the article, SIVmac: (Swiss-prot: P08810) and SIVsm: (Swiss-prot: P12492). The conserved aa (in red) are aa of the endocytosis signal (region A) and the aa at the end of the LLP-1 region (region G). The aa implicated in SIVmac NF-kB activation (end of region A) are absent in HIV-1 and its lineage (SIVcpz and gor).
Mentions: We divided the two final regions of our sequences in two arginine rich regions. The first region was a small LLP-3/LLP-1 inter-region (position 126 to 136 consensus RATRETLANAWR; region F, Table 3), and the second was the LLP-1 homologous sequence (position 137 to 165 consensuses GLWGALQRIGRGIL/AVPRRIRQGAELALL; with the final di-leucine motif; region G). The beginning of the LLP-1 region was highly variable (position 137 to 150, aa before the slash; G start, Table 3). This part contained also a lot of positions with mixtures of aa. In contrast, the end of the LLP-1 (aa after the slash) was the most constant part of the CT (G end, Table 3). Interestingly, this LLP-1 region was very rich in arginine and ended in all our sequences with the final di-leucine motif. Furthermore, the LLP-1 conserved part is also conserved among all primate lentiviruses (Figure 2).

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