A unified classification system for HIV-1 5' long terminal repeats

Area of Science:

• Virology
• Genetics
• Bioinformatics

Background:

• Human Immunodeficiency Virus type 1 (HIV-1) proviruses feature long terminal repeats (LTRs) essential for viral lifecycle stages.
• Existing classification systems for HIV-1 internal coding regions are established, but a systematic classification for 5' LTRs is lacking.
• This gap hinders comprehensive understanding of HIV-1 evolution, transmission, and therapeutic strategies.

Purpose of the Study:

• To establish a systematic and phylogenetic classification system for HIV-1 5' LTR sequences.
• To provide a unified framework for characterizing HIV-1 5' LTR diversity.
• To facilitate a deeper understanding of HIV-1 origin, spread, and potential therapeutic targets.

Main Methods:

• Analysis of available 5' LTR sequences from public databases.
• Application of 4 recognized principles for reference classification.
• Identification of representative and consensus sequences to define groups, subtypes, sub-subtypes, and circulating recombinant forms (CRFs).
• Validation of the classification system using clinical isolates from China.

Main Results:

• A classification system was supplemented, identifying 83 representative and 14 consensus sequences for 2 groups, 6 subtypes, 6 sub-subtypes, and 9 CRFs.
• Testing on 22 Chinese clinical isolates showed consistent classification for 16 strains.
• Six strains with recombination events in the 5' LTR exhibited altered subtype classification, impacting transcription factor binding sites (SP1, p53, NF-κB) and potentially affecting transcriptional activity.

Conclusions:

• A unified classification system for HIV-1 5' LTRs has been successfully supplemented.
• This system enhances the characterization of HIV-1 strains, particularly those with complex LTR structures.
• The findings are valuable for basic and clinical research, aiding in HIV-1 evolution studies and therapeutic development.