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IN VITRO REACTIVATION OF HUMAN IMMUNODEFICIENCY VIRUS-1 UPON STIMULATION WITH SCRUB TYPHUS RICKETTSIAL INFECTION

While a number of microbial infections induce a transient burst in viral load in individuals infected with human immunodeficiency virus-1 (HIV-1), a recent study has suggested that scrub typhus may suppress HIV-1 infection. We investigated the effects of Orientia tsutsugamushi on HIV-1 infection. In vitro HIV-1 infection experiments were conducted using peripheral blood mononuclear cells (PBMC) acutely infected with R5 and X4 HIV-1 or PBMC derived from patients receiving highly active antiretroviral therapy (HAART) whose plasma viral load was undetectable. Stimulation of PBMC with O. tsutsugamushi induced production of proinflammatory cytokines and ß-chemokines, and markedly down-regulated expression of CCR5. Although pretreatment with O. tsutsugamushi rendered PBMC resistant to R5 HIV-1, it otherwise enhanced HIV-1 replication. Stimulation by O. tsutsugamushi induced HIV-1 replication in PBMC from patients receiving HAART. These findings suggest that scrub typhus does not necessarily suppress HIV-1 infection and does have potential to enhance HIV-1 replication.

Received April 22, 2002. Accepted for publication January 20, 2003.

Acknowledgments: We thank A. S. Fauci for support, L. A. Ehler and S. B. Mizell for patient recruitment, and M. Yokoyama for technical assistance and graphic work.

Financial support: This work was supported in part by a grant provided by a Research for the Future Program (JSPS-RFTF97L00705) of the Japan Society for the Promotion of Science and by a Grant-in-Aid from the Ministry of Education, Science, Sports and Culture, Japan.

Authors’ addresses: Masako Moriuchi and Hiroyuki Moriuchi, Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan. Akira Tamura, Department of Microbiology, Niigata College of Pharmacy, Niigata 950-2076, Japan.

Reprint requests: Hiroyuki Moriuchi, Department of Pediatrics, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan, Telephone: 81-95-849-7297, Fax: 81-95-849-7301, E-mail: hiromori{at}net.nagasaki-u.ac.jp

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