Defective HIV proviruses: possible involvement in the HIV infection pathogenesis

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This review article analyzes information obtained from a literature search on defective HIV genomes (HIV-1, Human Immunodeficiency Virus, Lentivirus, Orthoretrovirinae, Retroviridae). It discusses the origins of defective HIV genomes, their potential for transcription and translation, and the role of defective RNA and proteins in stimulating both innate and adaptive immunity. The article also explores their contribution to HIV pathogenesis, immune system hyperactivation despite successful antiretroviral therapy (ART), and the evolutionary processes in HIV proviral populations under ART. Additionally, it addresses challenges in reservoir elimination and HIV eradication that arise from the existence of defective HIV viruses.

作者简介

Marina Bobkova

I. Mechnikov Research Institute for Vaccines and Sera

编辑信件的主要联系方式.
Email: mrbobkova@mail.ru
ORCID iD: 0000-0001-5481-8957

D.Sci. (Biol.), Chief Researcher of the laboratory of biology of lentiviruses

俄罗斯联邦, 105064, Moscow

参考

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2. Fig. 1. Causes of Defective HIV Virus Formation. a ‒ deletions in HIV genome fragments; b ‒ G→A hypermutations, illustrated with APOBEC3G; c ‒ insertions; d ‒ stop codons; e ‒ mechanical DNA damage.

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3. Fig. 2. Contribution of Host Cell Restriction Factors to the Formation of Mutations in the HIV Genome During Reverse Transcription. a ‒ APOBEC3G – a cytidine deaminase; b ‒ SAMHD1 – a phosphohydrolase.

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4. Fig. 3. Splicing Variants of Full-Length HIV RNA.

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5. Fig. 4. HIV RNA and DNA Molecules as Stimulators of Innate Immunity. DNA sensors: IFI16 and the cGAS-STING complex; RNA sensors: MAVS and RIG-1; IRF3 – interferon regulatory factor.

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6. Fig. 5. Formation of the Cellular Immune Response to Intact and Defective HIV Proteins.

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7. Fig. 6. Origin of HIV Viral Particles. a ‒ ongoing HIV replication with repeated infection cycles; b ‒ clonal expansion followed by periodic activation of the provirus.

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8. Fig. 7. Variability of HIV and Provirus Integration Sites Under Conditions of ongoing replication (a); clonal expansion (b).

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9. Fig. 8. Effect of the Genomic Context of the HIV Provirus on Transcription Efficiency. a ‒ integration into a euchromatic region; b ‒ integration into a heterochromatic region of the human genome.

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10. Fig. 9. Key Events in the Evolution of the HIV Proviral Population. a ‒ the period from infection to the start of ART; b‒d ‒ clonal expansion as the main source of HIV; c ‒ selection of proviruses integrated into heterochromatic regions of the host genome; d ‒ selection of defective proviruses. Stages C and D occur in parallel.

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