期刊
JOURNAL OF INFECTIOUS DISEASES
卷 225, 期 2, 页码 317-326出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiab202
关键词
HIV-1; HTLV-1; coinfection; integration site analysis; high-throughput sequencing
资金
- Japan Society for the Promotion of Science KAKENHI [JP16K19580, JP16KK0206, JP18K16122, JP20H03724]
- Japan Agency for Medical Research and Development [JP20wm0325015, JP20jm0210074, JP20fk0410023, JP16H06277]
- Friends of Leukemia Research Fund
- International Joint Usage/Research Center, the Institute of Medical Science, the University of Tokyo
- Kumamoto University Excellent Research Projects grant
Coinfection with HIV-1 and HTLV-1 alters the distribution of viral integration sites and clonality of virus-infected cells, potentially impacting the risks associated with both HTLV-1 and HIV-1-related diseases.
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.
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