The Discovery of HTLV

In 1976, the first key event of the HTLV virus was the discovery of Adult T-cell Leukemia/Lymphoma (ATLL) in Japan, led by Takatsuki and his colleagues. There were reports of unique characteristics of leukemia with unusual morphology of leukemic cells (Uchiyama et al., 1977), subsequently, Takatsuki's findings confirmed that the identified ATLL patients originated from Kyushu (West part of Japan), was an endemic area.

At the NIH, Robert C Gallo and his co-workers discovered and identified the virus from a patient with Mycosis fungoides infection with ATLL (Poiesz et al., 1980). Despite the fact that Gallo discovered the virus, he was unable to prove that the virus actually caused leukemia/lymphoma. Further progress in understanding the virus and its role in T-cell malignancies came from the information provided by Waldmann and Uchiyama during their epidemiology studies of ATLL in Japan. Later on, the description of several isolates of the virus, its characteristics, along with the evidences of integrated provirus, and positive serological results tested in US and Japanese ATLL patients, was published by Gallo, 1981 to provide clear support for the linkage of the virus to T-cell malignancies.

Molecular applications provided further identification of the virus in Japan, by Yoshida et al. The results were reported as adult T-cell leukemia virus (ATLV) in 1982.

Through a series of molecular and immunological comparison studies between ATLL patients' sera samples from Japan (Hinuma et al., 1981) and Gallo's isolated virus, they found that the virus, ATLV and the disease, ATLL are associated. The findings from the Japanese and US demonstrated both the viruses were identical at the molecular level and named as HTLV-I virus (Watanabe et al., 1984).

In 1982, Gallo isolated a closely related HTLV-I subtype known as HTLV-II, from a patient with an unidentified T cell lymphoproliferative disease possessing characteristics similar to the B cell disorder, hairy cell leukemia that was reported in 1982 (Kalyanaraman et al., 1982). It shares approximately 70% genomic homology and structural similarity with HTLV-I. The HTLV-II virus is found predominantly in IV drug users and Native Americans, as well as the Caribbean and South American Indian groups.

In 2005, Mahieux, Gessain and CDC laboratories (Mahieux et al., 2009) discovered and found two other HTLV subtypes, HTLV-III and HTLV-IV in rural Cameroon. They hypothesized that these viruses evolved via interspecies-transmitted from STLV-3/4 infected monkeys to humans through sexual activity or breastfeeding (Mahieux et al., 2009). There were very few reports about these two subtypes, and have yet to know how much further transmission has occurred among humans, or whether the viruses can cause diseases. Although the knowledge of pathogenicity is very little, several lines of molecular evidences suggest that HTLV-3 possesses some of the HTLV-I properties. Future studies will enable researchers to understand if the HTLV-III and HTLV-IV viruses will become an emerging infectious disease.

Mahieux et. al. The human HTLV-3 and HTLV-4 retroviruses: New members of the HTLV family. Patholgie Biologie 2009;57:161-166
Calattini et al. New Strain of Human T Lymphotropic Virus (HTLV) Type 3 in a Pygmy from Cameroon with Peculiar HTLV Serologic Results JID 2009;199:561-564
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