Human T-lymphotropic virus 1

HTLV-1 is a retrovirus belonging to the family retroviridae and the genus deltaretrovirus. It has a positive-sense RNA genome that is reverse transcribed into DNA and then integrated into the cellular DNA. Once integrated, HTLV-1 continues to exist only as a provirus which can spread from cell to cell through a viral synapse. Few, if any, free virions are produced and there is usually no detectable virus in the blood plasma though the virus is present in genital secretions. Like HIV, HTLV-1 predominantly infects CD4+ T cells.[8]

The viral RNA is packed into the icosahedral capsid which is contained inside the protein inner envelope. The lipid outer envelope is of host cell origin but contains viral transmembrane and surface proteins. The virion is spherical in shape with a diameter of about 100 nm.[8]

HTLV-1 is genetically classified into seven subtypes, each defined by a unique geographic distribution influenced by population migration. The most globally widespread is the cosmopolitan subtype A, which further branches into several subgroups: transcontinental, Japanese, West African, North African, Senegalese, and Afro-Peruvian.[9] While subtypes B, D, E, F, and G are localized to distinct regions in Africa, subtype C is predominant in Australia and Oceania.[10]

HTLV-1 is believed to have originated from the simian T-lymphotropic virus type 1 (STLV-1), a retrovirus prevalent among numerous nonhuman primates in intertropical Africa. This theory is supported by the significant genetic diversity of HTLV-1 subtypes in Africa, potentially arising from repeated zoonotic transmissions during human interactions with STLV-1 endemic nonhuman primates. This correlation is further reinforced by the observation that individuals bitten by nonhuman primates exhibit HTLV-1 strains with sequences remarkably homologous to the STLV-1 found in local primate species.[11]

The global distribution of HTLV-I is highly heterogeneous, with focal occurrence in diverse regions. Within areas where HTLV-I is found, its occurrence varies considerably, with endemic clusters often situated near populations with lower prevalence. This pattern might be influenced by the founder effect, suggesting prolonged viral transmission within isolated groups, but this theory warrants further investigation. Consistent findings reveal that HTLV-1 prevalence increases with age and is usually higher in adult females than males. Areas broadly regarded as having endemic regions include Japan, Iran, the Americas, the Caribbean, Melanesia, Central and West Africa, and Australia. Globally, their remains a lack of robust data from populous countries like India and Nigeria and most of North and East Africa. As such, current global prevalence estimates, which are based on known endemic regions, likely underestimate the true global prevalence.[1]

In Australia, HTLV-I has notably high prevalence among Aboriginal communities in Central Australia. Community-based cross-sectional studies from Central Australia report HTLV-1 prevalences exceeding 30%, representing the highest reported prevalence for any population worldwide.[12] In Taiwan, in Iran, and in Fujian (a Chinese province near Taiwan) the prevalence is 0.1–1%. The infection rate is about 1% in Papua New Guinea, the Solomon Islands, and Vanuatu, where the genotype C predominates. In Europe HTLV-1 is uncommon, although it is present in some populations, generally people who have migrated from known endemic regions. In the Americas HTLV-1 is found in some Indigenous populations and descendants of African ancestry from where it is thought to have originated. Prevalence ranges from 0.1 to 1%. In Africa the prevalence is not well known, but it is about 1% in some countries {{Citation needed}}.[8]

HTLV-I infection in the United States appears to be about half as prevalent among IV drug users and about one-tenth as prevalent in the population at large as HIV infection {{Citation needed}}. Although little serologic data exist, the prevalence of infection is thought to be highest among blacks living in the Southeast {{Citation needed}}. A prevalence rate of 30% has been found among black intravenous drug users in New Jersey, and a rate of 49% has been found in a similar group in New Orleans.[13] {{Citation needed|reason=Prevalence is not a rate. Additionally, the citation references an old study that did not discriminate between HTLV-1 or HTLV-2, which has substantially different pathologic, and transmission characteristics. |date=October 2023}}

It is also high among the Inuit of Northern Canada, in Japan, northeastern Iran.[14] Peru, the Pacific coast of Colombia and Ecuador, and the Caribbean.

HTLV-1 has three main routes of transmission. Vertical transmission is most common, through which an infected mother transmits the virus to her child {{Citation needed|reason=Sexual transmission is the most common, hence increasing prevalence with age|date=October 2023}}. Interestingly, the risk to a fetus while inside the womb is minimal, given the virtual absence of viral particles in human plasma. Most vertical infection occurs through breastfeeding. About 25% of infants who are breastfed by infected mothers are infected, while less than 5% of children born to but not breastfed by infected mothers are infected. Sexual transmission is second-most common, whereby an individual infects another through exchange of bodily fluids. Some evidence has suggested that male-to-female transmission is more efficient than female-to-male transmission. For example, one study in Japan found a 61% transmission rate for males to females vs. a less than 1% rate for females to males. Least common is parenteral transmission through blood transfusion, with an infection rate of 44-63% estimated in one study, and needle sharing among intravenous drug users. With proper prophylaxis (e.g. breastfeeding counseling for mothers, condom use, and donor blood screening), rates of transmission can be effectively reduced.[15] The importance of the various routes of transmission is believed to vary geographically. The research in discordant couples showed that probability of sexual transmission is about 0.9 per 100 person-years.[8]

• In Japan, the geographic clustering of infections suggest that the virus is more dependent on mother-to-child transmission.[16]
• In the Caribbean, the geographic distribution of the virus is more uniform, and it is more common among those with many sexual partners, indicating that sexual transmission is more common.[17]

The term viral tropism refers to which cell types HTLV-I infects. Although HTLV-1 is primarily found in CD4+ T cells, other cell types in the peripheral blood of infected individuals have been found to contain HTLV-1, including CD8+ T cells, dendritic cells and B cells. HTLV-I entry is mediated through interaction of the surface unit of the virion envelope glycoprotein (SU) with its cellular receptor GLUT1, a glucose transporter, on target cells.[18]

Treatment of opportunistic infections varies depending on the type of disease and ranges from careful observation to aggressive chemotherapy and antiretroviral agents. Adult T cell lymphoma is a common complication of HTLV infection and requires aggressive chemotherapy, typically R-CHOP. Other treatments for ATL in HTLV infected patients include interferon alpha, zidovudine with interferon alpha and CHOP with arsenic trioxide. Treatments for HTLV myelopathy are even more limited and focus mainly on symptomatic therapy. Therapies studied include corticosteroids, plasmapheresis, cyclophosphamide, and interferon, which may produce a temporary symptomatic improvement in myelopathy symptoms.[20]

Valproic acid has been studied to determine if it might slow the progression of HTLV disease by reducing viral load. Although in one human study it was effective in reducing viral load, there did not appear to be a clinical benefit. Recently however, a study of valproic acid combined with zidovudine showed a major decrease in the viral load of baboons infected with HTLV-1. It is important to monitor HTLV patients for opportunistic infections such as cytomegalovirus, histoplasmosis, scabies, pneumocystis pneumonia, and staphylococcal infections. HIV testing should also be performed, as some patients may be co-infected with both viruses.

Allogenic bone marrow transplantation has been investigated in the treatment of HTLV-1 disease with varied results. One case report describes an HTLV-1 infected woman who developed chronic refractory eczema, corneal injury and adult T cell leukemia. She was subsequently treated with allogenic stem cell transplantation and had complete resolution of symptoms. One year post-transplant, she has had no recurrence of any symptoms, and furthermore has had a decrease in her proviral load.

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• International Retrovirology Association
• Human+T-lymphotropic+virus+1 at the U.S. National Library of Medicine Medical Subject Headings (MeSH)