Clonality of HIV-1– and HTLV-1–Infected Cells in Naturally Coinfected Individuals

• Published in: The Journal of infectious diseases Vol. 225; no. 2; pp. 317 - 326
• Main Authors: Katsuya, Hiroo, Cook, Lucy B M, Rowan, Aileen G, Melamed, Anat, Turpin, Jocelyn, Ito, Jumpei, Islam, Saiful, Miyazato, Paola, Jek Yang Tan, Benjy, Matsuo, Misaki, Miyakawa, Toshikazu, Nakata, Hirotomo, Matsushita, Shuzo, Taylor, Graham P, Bangham, Charles R M, Kimura, Shinya, Satou, Yorifumi
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 15.01.2022
• Subjects: Blood tests; CD4 antigen; CD4 Lymphocyte Count; Central nervous system diseases; Coinfection; Comorbidity; Deoxyribonucleic acid; Diagnostic tests; DNA; High-Throughput Nucleotide Sequencing; HIV; HIV Infections - complications; HIV Infections - epidemiology; HIV-1 - genetics; HIV-1 - isolation & purification; HTLV-I Infections - complications; HTLV-I Infections - epidemiology; Human immunodeficiency virus; Human T-lymphotropic virus 1 - genetics; Human T-lymphotropic virus 1 - isolation & purification; Humans; Leukemia; Life Sciences; Lymphocytes T; Microbiology and Parasitology; Next-generation sequencing; Paraparesis, Tropical Spastic - diagnosis; Paraparesis, Tropical Spastic - epidemiology; Peripheral blood; Polymerase chain reaction; Proviruses - genetics; Real-Time Polymerase Chain Reaction; Spinal cord; Transcription; Virology; Viruses; HIV-1; HTLV-1; integration site analysis; coinfection; high-throughput sequencing
• DOI: 10.1093/infdis/jiab202
• ISSN: 0022-1899; 1537-6613

Abstract Background Coinfection with human immunodeficiency virus type 1 (HIV-1) and human T-cell leukemia virus type 1 (HTLV-1) diminishes the value of the CD4+ T-cell count in diagnosing AIDS, and increases the rate of HTLV-1–associated myelopathy. It remains elusive how HIV-1/HTLV-1 coinfection is related to such characteristics. We investigated the mutual effect of HIV-1/HTLV-1 coinfection on their integration sites (ISs) and clonal expansion. Methods We extracted DNA from longitudinal peripheral blood samples from 7 HIV-1/HTLV-1 coinfected, and 12 HIV-1 and 13 HTLV-1 monoinfected individuals. Proviral loads (PVL) were quantified using real-time polymerase chain reaction (PCR). Viral ISs and clonality were quantified by ligation-mediated PCR followed by high-throughput sequencing. Results PVL of both HIV-1 and HTLV-1 in coinfected individuals was significantly higher than that of the respective virus in monoinfected individuals. The degree of oligoclonality of both HIV-1– and HTLV-1–infected cells in coinfected individuals was also greater than in monoinfected subjects. ISs of HIV-1 in cases of coinfection were more frequently located in intergenic regions and transcriptionally silent regions, compared with HIV-1 monoinfected individuals. Conclusions HIV-1/HTLV-1 coinfection makes an impact on the distribution of viral ISs and clonality of virus-infected cells and thus may alter the risks of both HTLV-1– and HIV-1–associated disease. We investigated the mutual effect of HIV-1/HTLV-1 coinfection on their integration sites and the clonal expansion and found the degree of oligoclonality of both HIV-1– and HTLV-1–infected cells in coinfected individuals was greater than that in monoinfected subjects.