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

Hiroo Katsuya; Lucy B M Cook; Aileen G Rowan; Anat Melamed; Jocelyn Turpin; Jumpei Ito; Saiful Islam; Paola Miyazato; Benjy Jek Yang Tan; Misaki Matsuo; Toshikazu Miyakawa; Hirotomo Nakata; Shuzo Matsushita; Graham P Taylor; Charles R M Bangham; Shinya Kimura; Yorifumi Satou

doi:10.1093/infdis/jiab202

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

J Infect Dis. 2022 Jan 18;225(2):317-326. doi: 10.1093/infdis/jiab202.

Authors

Hiroo Katsuya^{1

2}, Lucy B M Cook³, Aileen G Rowan³, Anat Melamed³, Jocelyn Turpin³, Jumpei Ito⁴, Saiful Islam^{2

5}, Paola Miyazato^{2

5}, Benjy Jek Yang Tan^{2

5}, Misaki Matsuo^{2

5}, Toshikazu Miyakawa⁶, Hirotomo Nakata⁶, Shuzo Matsushita⁷, Graham P Taylor³, Charles R M Bangham³, Shinya Kimura¹, Yorifumi Satou^{2

5}

Affiliations

¹ Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan.
² Division of Genomics and Transcriptomics, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan.
³ Department of Infectious Diseases, Faculty of Medicine, Imperial College London, London, UK.
⁴ Division of Systems Virology, Department of Infectious Disease Control, International Research Center for Infectious Diseases, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
⁵ International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Japan.
⁶ Department of Hematology, Rheumatology and Infectious Diseases, Kumamoto University of Medicine, Kumamoto, Japan.
⁷ Clinical Retrovirology, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan.

PMID: 33844021
DOI: 10.1093/infdis/jiab202

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.

Keywords: HIV-1; HTLV-1; coinfection; high-throughput sequencing; integration site analysis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

CD4 Lymphocyte Count
Coinfection*
HIV Infections / complications*
HIV Infections / epidemiology
HIV-1* / genetics
HIV-1* / isolation & purification
HTLV-I Infections / complications*
HTLV-I Infections / epidemiology
High-Throughput Nucleotide Sequencing
Human T-lymphotropic virus 1* / genetics
Human T-lymphotropic virus 1* / isolation & purification
Humans
Paraparesis, Tropical Spastic / diagnosis
Paraparesis, Tropical Spastic / epidemiology*
Proviruses / genetics
Real-Time Polymerase Chain Reaction

Abstract

Publication types

MeSH terms

Grants and funding