Human T-Cell Lymphotropic Virus Type I

Introduction

Human T- Lymphotropic Virus Type I, also known as human T-cell lymphotropic virus type I, or human T-cell-leukemia-lymphoma virus, or HTLV-1 is an oncogenic retrovirus from a family of HTLV that can be sexually transmitted and has been associated with various diseases, including adult T-cell leukemia/lymphoma, as well as HTLV-associated myelopathy (also known as spastic paraparesis or HAM/TSP) . Reported independently by Robert C. Gallo in 1980 and Yorio Hinuma in 1981 , it is the first human retrovirus discovered, preceding HIV 1 and 2. The HTLV family is categorized into a larger group known as primate T-lymphotropic viruses (PTLVs) that include HTLVs, which infect humans, and Simian T-lymphotropic viruses (STLVs), which infects Old World monkeys. The HTLVs is also closely related to the bovine leukemia virus, responsible for a zoonotic infection that is widespread in domesticated cattle. There are currently 4 known types of HTLVs: HTLV-1, HTLV-2, HTLV-3, and HTLV-4. Strains HTLV-1 and HTLV-2 have been the most prevalent worldwide, while the effects of the latter two strains on human populations still remain unclear. The HTLVs most likely originated from cross-species transmission of the STLVs.

HTLVs target particularly T-cells, a lymphocyte that plays a crucial role in the human immune system. The HTLV-1 genome is diploidal, consisting of two copies of single-stranded RNA virus which are both turned into a double-stranded DNA form that is integrated into the genome of the host cell. After integration, HTLV uses components of the host cell to create more viral particles.

The majority of HTLV-infected individuals live asymptomatically and never face complications. It is not fully understood yet the progression of HTLV from asymptomatic to symptomatic state. Japan, as well as the Caribbean islands, Central Africa, the Middle East, Central and South America, and Melanesia, are known endemic areas of HTLV.

Discovery of the First Human Retrovirus

HTLV-1 was first detected and isolated by Robert C. Gallo from an analysis of a T cell line from a patient with cutaneous t cell lymphoma. After a reverse transcriptase (RT) assay performed on the cells found positive results, electron microscopy was performed as well and found retrovirus particles present in the concentrated RT. To ensure that these particles are actually evidence of a human retrovirus and not from accidental laboratory contaminants like previous researches on the subject unfortunately found, Gallo had to prove that:

1) identical virus could be isolated from a primary tissue sample obtained from the same patient by using primary T cell with Interleukin-2, a particular cytokine secreted by lymphocytes in the human immune system,
2) the virus was new and not a form of any previously discover animal retroviruses,
3) capable of infecting human T cells in vitro,
4) there are specific antibodies to the virus present in the serum of the patient,
5) integration of proviral DNA in the DNA of the cell in which the virus was isolated
6) provide serological evidence that those specific antibodies

In March 1981, Gallo and Colleague presented their results in a meeting with several other Japanese scientists, including Takatsuki and his co-workers. Hoping to address the prevalence of Adult T-cell Leukemia (ATL) in southern Japan. During this meeting, they reviewed several isolates of HTLV-1, along with reverse transcriptase proteins, evidence of HTLV-1 integration and linkage to T cell malignancies, and supporting serological results from Japanese ATL patients. Comparisons from this meeting were summarized and published in November 1981.

Dr. Yorio Hinuma, a researcher who was personally infected with the retrovirus, also presented his research on ATL cells and established isolates which he called Adult T cell leukemia virus (ATLV) shortly after. He objected to collaboration with American scientists due to “cultural reasons,” but a later comparative analysis of ATLV and HTLV isolates confirmed that these two isolates were indeed the same virus.

Subsequent research shows that HTLV-1 infections are endemic in other regions, as well. Dr. Daniel Catovsky, a British hematologist, found an unusually high occurrence of ATL in immigrants from the Caribbean Islands to England. Following more highly specified research in the region, the endemicity was narrowed down to distinctive tribes in Africa as well as the Caribbean. In 1981, Dr. Gallo and colleagues isolated another less pathogenic strain from the same HTLV family, called HTLV-2. HTLV-2 was isolated from another form of leukemia called Hairy Cell Leukemia.

References

Edited by Rachel Chen, student of Joan Slonczewski for BIOL 116 Information in Living Systems, 2020, Kenyon College.