HIV-1 subtype C Tat exon-1 amino acid residue 24K is a signature for neurocognitive impairment.
J Neurovirol
; 28(3): 392-403, 2022 06.
Article
en En
| MEDLINE
| ID: mdl-35394614
ABSTRACT
Variation and differential selection pressures on Tat genes have been shown to alter the biological function of the protein, resulting in pathological consequences in a number of organs including the brain. We evaluated the impact of genetic variation and selection pressure on 147 HIV-1 subtype C Tat exon 1 sequences from monocyte-depleted peripheral lymphocytes on clinical diagnosis of neurocognitive impairment. Genetic analyses identified two signature amino acid residues, lysine at codon 24 (24K) with a frequency of 43.4% and arginine at codon 29 (29R) with a frequency of 34.0% in individuals with HIV-associated neurocognitive impairment. The analyses also revealed two signature residues, asparagine, 24 N (31.9%), and histidine, 29H (21.3%), in individuals without neurocognitive impairment. Both codons, 24 and 29, were associated with high entropy but only codon 29 was under positive selection. The presence of signature K24 increased by 2.08 times the risk of neurocognitive impairment, 3.15 times higher proviral load, and 69% lower absolute CD4 T-cell count compared to those without the signature. The results support a linkage between HIV-1 C Tat N24K polymorphism, proviral load, immunosuppression, and neurocognitive impairment. The signature may induce more neurotoxic effects, which contributes to establishment and severity of HIV-associated neurocognitive impairment.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Infecciones por VIH
/
VIH-1
/
Productos del Gen tat del Virus de la Inmunodeficiencia Humana
/
Disfunción Cognitiva
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Neurovirol
Asunto de la revista:
NEUROLOGIA
/
VIROLOGIA
Año:
2022
Tipo del documento:
Article
País de afiliación:
Sudáfrica