The Discovery of HTLV

The Human T- Lymphotropic Virus (HTLV) was isolated, from an African-American with a T-cell lymphoma infiltrating his skin, in 1980 by Dr Poiesz and others in the laboratory of Dr Gallo1.

 

In 1982 the same group identified a related virus from lymphocytes which they called HTLV-II2.

 

In 1983, two research teams, one in France and Dr. Gallo's team in the USA found the causative agent of the then newly-described condition Acquired Immunodeficiency Syndrome. Barré-Sinoussi's team called this virus LAV (lymphadenopathy associated virus) whilst Gallo's team called it HTLV-III because of key similarities to HTLVs.  However, this virus was found to belong to a different family of retroviruses and was renamed Human Immunodeficiency Virus (HIV).

 

It is important not to confuse HIV-1 with HTLV-1 despite the similarity in the name.

 

HTLV-1 and the closely related HTLV-2 were the first discovered human retroviruses.

 

Earlier, in Japan, Professor Uchiyama3 had newly described a distinct blood malignancy, most common in Southwest Japan, Adult T-cell Leukaemia, which could manifest as either a lymphoma or a leukaemia (ATL). At the same time as Gallo’s team were researching HTLV Miyoshi and colleagues isolated the adult T-cell leukaemia virus (ATLV) from a patient with ATL4; the genetic code of this virus was then shown to be almost identical to the original HTLV-I isolate; families of patients with ATL had antibodies to HTLV-1.

 

The first description of ATL outside of Japan was by Professor Dani Catovsky5 at the Royal Marsden Hospital, London who in 1982 described six patients with this new disease and noted that they originated from the West Indies.

 

Amongst other characteristics the cells in this disease had a distinctive lobulated nucleus-giving rise to their name, 'Flower cells'.

 

There followed an exodus of researchers to these islands, including a French medical student who travelled to Martinique to see how common HTLV-1 was. Having investigated Haematology patients he chose patients on the Neurology ward as a control group and was surprised to find that 85% of patients diagnosed with Tropical Spastic Paraparesis (TSP) had antibodies against HTLV-1 indicating that they were infected with this virus6 and in Japan Professor Osame was describing patients with HTLV-I infection and spinal cord inflammation (HTLV-1-associated myelopathy, HAM) similar to TSP7.

 

Understanding How HTLV Causes Disease

Whilst being a carrier of this virus is essential for the development of both ATL and HAM it is clearly not sufficient – given that 90% of carriers develop neither disease. Several studies clearly indicate that that amount of virus in the blood – the viral burden – is important but again not sufficient.

One focus of our research at the moment is to identify the next key component in disease development with a view to identifying those most at risk of disease for closer monitoring and eventually for treatment of the infection to prevent disease. In addition to high viral burden we have identified activation of particular white blood cells as a risk for developing HAM and expansion of particular populations of white blood cells as a risk of ATL8. At the moment prevention of disease is only a theory but an intervention study is in the early stages of design.

 

 

References

1. Poiesz BJ, Ruscetti FW, Gazdar AF, Bunn PA, Minna JD, Gallo RC. Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc Natl Acad Sci U S A. 1980;77(12):7415-9.

2. Kalyanaraman VS, Sarngadharan MG, Robert-Guroff M, Miyoshi I, Golde D, Gallo RC. A new subtype of human T-cell leukemia virus (HTLV-II) associated with a T-cell variant of hairy cell leukemia. Science. 1982;218:571-3.

3. Uchiyama T, Yodoi J, Sagawa K, Takatsuki K, Uchino H. Adult T-cell Leukaemia: clinical and haematological features of 16 cases. Blood. 1977;50:481-92.

4. Miyoshi I, Kubonishi I, Yoshimoto S, Akagi T, Ohtsuki Y, Shiraishi Y, et al. Type C virus particles in a cord T-cell line derived by co-cultivating normal human cord leukocytes and human leukaemic T cells. Nature. 1981;294(5843):770-1.

5. Catovsky D, Greaves MF, Rose M, Galton DA, Goolden AW, McCluskey DR, et al. Adult T-cell lymphoma-leukaemia in Blacks from the West Indies. Lancet. 1982;1(8273):639-43.

6. Gessain A, Barin F, Vernant JC, Gout O, Maurs L, Calender A, et al. Antibodies to human T-lymphotropic virus type-I in patients with tropical spastic paraparesis. Lancet. 1985;2(8452):407-10.

7. Osame M, Usuku K, Izumo S, Ijichi N, Amitani H, Igata A, et al. HTLV-I associated myelopathy, a new clinical entity. Lancet. 1986;1(8488):1031-2.

8. Kagdi H, Demontis MA, Ramos JC, Taylor GP. Switching and loss of cellular cytokine producing capacity characterize in vivo viral infection and malignant transformation in human T- lymphotropic virus type 1 infection. PLoS Pathog. 2018;14(2):e1006861.