Human T-cell leukemia virus 3 (HTLV‑3) is a human retrovirus classified within the genus Deltaretrovirus. It was first detected in 2005 in two asymptomatic individuals from southern Cameroon. HTLV‑3 is genetically most similar to simian T‑cell lymphotropic virus type 3 (STLV‑3) and is thought to have arisen by zoonotic transmission from African monkeys. The enveloped virion contains two identical copies of a positive‑sense single‑stranded RNA genome of approximately 9 kb that is reverse transcribed into DNA and integrated into the host genome. The virus encodes structural proteins (Gag, Pol, Env) and regulatory proteins such as Tax and accessory proteins with sequences distinct from HTLV‑1/2.
Genomic Features and Origin
HTLV‑3 shares about 60–65 % nucleotide identity with HTLV‑1 and HTLV‑2 but is more closely related to STLV‑3 strains circulating in Central African monkeys. Its genome contains long terminal repeats flanking the coding region and an internal coding region with gag, pol and env genes as well as regulatory and accessory open reading frames. The Tax‑3 protein retains motifs involved in transcriptional activation of viral and host genes but differs substantially from Tax‑1 and Tax‑2, suggesting divergent pathogenic potential. Only a handful of HTLV‑3 isolates have been sequenced, and their proviral genomes show evidence of zoonotic acquisition rather than long‑term human adaptation. Entry receptors have not been definitively determined, but studies suggest that HTLV‑3 may use a similar combination of glucose transporter 1, neuropilin‑1 and heparan sulphate proteoglycans as other deltaretroviruses.
Discovery and Public Health Relevance
The initial HTLV‑3 cases were discovered during a survey of hunters in Cameroon who had been exposed to non‑human primate blood and tissues. These individuals harboured antibodies that cross‑reacted with HTLV‑1/2 antigens, and PCR analysis revealed a novel provirus closely related to STLV‑3. Subsequent serosurveys have identified very few additional cases, and all infected individuals have been asymptomatic. No clear association with leukaemia, lymphoma or neurologic disease has been documented. Because HTLV‑3 is rare and appears confined to populations with close contact to primates, its public health impact is currently minimal. Nevertheless, its existence highlights the potential for cross‑species transmission of retroviruses through bushmeat hunting and underscores the need for surveillance of zoonotic retroviral infections. Screening blood donors in endemic regions and educating hunters may help reduce future spillover events. The identification of HTLV‑3 expands the diversity of human deltaretroviruses and provides a valuable opportunity to study early events in cross‑species transmission. Continued monitoring and genomic analysis will help clarify whether this virus establishes wider human transmission or remains a rare zoonotic infection. Related Terms: Human T‑Cell Leukemia Virus 1, Human T‑Cell Leukemia Virus 2, Human T‑Cell Leukemia Virus 4, Simian T‑Cell Lymphotropic Virus 3, Human Immunodeficiency Virus 1