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In vitro infection of human macrophages by human T-cell leukemia/lymphotropic virus type I (HTLV-I)
I J Koralnik1, J F Lemp, R C Gallo
1Laboratory of Tumor Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Abstract:
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-ICR and HTLV-IBOU 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 p40tax and p27rex proteins, as well as the p12I, and p30II 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.
Insights
Human T-lymphotropic virus type I (HTLV-I) can replicate in primary human macrophages. This finding suggests a potential role for macrophages in HTLV-I spread within the nervous system.
Area of Science:
- Virology
- Neuroimmunology
- Cell Biology
Background:
- Human T-lymphotropic virus type I (HTLV-I) is linked to Tropical Spastic Paraparesis/HTLV-I associated myelopathy (TSP/HAM), a neurological condition.
- The role of macrophages in HTLV-I dissemination within the central nervous system is not fully understood.
Purpose of the Study:
- To investigate the replication capacity of HTLV-I in primary human macrophages.
- To determine if macrophages can serve as a host for HTLV-I infection and viral production.
Main Methods:
- Infection of elutriated human macrophages with HTLV-I isolates (HTLV-ICR and HTLV-IBOU).
- Monitoring viral production via p24 gag antigen assays, electron microscopy (EM), and polymerase chain reaction (PCR).
- Detection of viral DNA, RNA, and spliced mRNAs (p40tax, p27rex, p12I, p30II) in infected cells.
Main Results:
- HTLV-I p24 gag antigen was detected in cell culture supernatants 21 days post-infection.
- Mature viral particles were observed via EM one month after infection.
- Viral sequences and spliced mRNAs encoding key viral proteins were identified in infected macrophages.
Conclusions:
- Primary human macrophages support HTLV-I replication in vitro.
- Macrophage infection by HTLV-I is a potential mechanism for viral dissemination in the body.
- Further research is needed to confirm in vivo macrophage infection and its role in TSP/HAM pathogenesis.
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