Human T-cell leukemia virus 4 (HTLV‑4) is a rare human retrovirus in the genus Deltaretrovirus. It was described in 2005 from the blood of a healthy adult man in southern Cameroon. Molecular analysis showed that the virus is closely related to simian T‑cell lymphotropic virus type 4 (STLV‑4) identified in western lowland gorillas, suggesting a zoonotic origin. HTLV‑4 particles are enveloped and contain two copies of a positive‑sense single‑stranded RNA genome of approximately 9 kb. Like other deltaretroviruses, the RNA is reverse transcribed into DNA and integrated into the host genome, allowing persistent infection. The virus encodes structural proteins (Gag, Pol, Env) and regulatory proteins, but its accessory genes differ from those of HTLV‑1 and HTLV‑2.
Genomic Characterisation and Transmission
HTLV‑4 has long terminal repeats flanking its genome and open reading frames encoding core retroviral proteins. Sequence comparisons show that its gag, pol and env genes are most closely related to STLV‑4, while the regulatory region contains unique motifs. The virus appears to use receptor complexes similar to other HTLVs, but experimental data are limited. HTLV‑4 DNA was detected at low proviral load in peripheral blood mononuclear cells of the index case, indicating low replicative activity. No additional human cases have been convincingly documented. It is presumed that infection occurred through exposure to gorilla blood or tissues during hunting or butchering, and there is no evidence of subsequent human‑to‑human transmission. The ability of HTLV‑4 to spread efficiently between people remains unknown.
Current Knowledge and Significance
The single reported HTLV‑4 carrier remained clinically healthy, and no associated malignancy or neurologic disease has been linked to this virus. Because of its rarity, epidemiologic data are unavailable, and disease associations cannot be confidently assessed. Nevertheless, the discovery of HTLV‑4 underscores the ongoing risk of cross‑species transmission of retroviruses from non‑human primates to humans. Surveillance studies of bushmeat hunters and primate workers in Central Africa have since focused on detecting STLV and HTLV infections. Preventive measures include avoiding contact with primate blood and tissues, using protective equipment when handling wildlife and screening blood donors in regions where primate exposure is common. Further research is needed to understand the biology of HTLV‑4 and its potential to adapt to humans. HTLV‑4 represents the fourth recognised human deltaretrovirus, extending our understanding of retroviral diversity. While its pathogenic potential is uncertain, its identification highlights the importance of monitoring zoonotic viruses at the human–animal interface. Related Terms: Human T‑Cell Leukemia Virus 1, Human T‑Cell Leukemia Virus 2, Human T‑Cell Leukemia Virus 3, Simian T‑Cell Lymphotropic Virus 4, Human Immunodeficiency Virus 1