In Vitro Infection of Human Macrophages by Human T-Cell Leukemia/Lymphotropic Virus Type I (HTLV-I)

HTLV-I is associated with a neurological syndrome designated Tropical Spastic Paraparesis/HTLV-I associated myelopathy (TSP/HAM). To determine whether HTLV-I can replicate in human primary macrophages and thus contribute to HTLV-I dissemination in the nervous system, elutriated human macrophages were infected cell-free with the HTLV-I_CR and HTLV-I_BOU isolates from patients with adult T-cell leukemia and TSP/HAM, respectively. Viral production was monitored by measuring the viral p24 gag antigen in the cell culture supernatant, by electron microscopy (EM) and by polymerase chain reaction (PCR) on viral DNA and RNA. The HTLV-I p24 gag antigen was detected 21 days after infection with either isolate, and the presence of mature viral particles was demonstrated by electron microscopy one month after infection. Viral sequences were amplified by PCR analysis of the infected macrophages’ DNA. Spliced mRNAs for the p40^tax and p27^rex proteins, as well as the p12^I, and p30^II proteins encoded by the pX region were readily identified by reverse transcriptase PCR. Altogether, these data indicate that HTLV-I replication occurs in vitro in primary human macrophages. Whether macrophage infection occurs also in vivo and is a crucial step in the induction of the neurological manifestations observed in TSP/HAM remains an open question.