Human T-lymphotropic virus

Overview
Human T-lymphotropic virus (HTLV) is a human, single-stranded RNA retrovirus that causes T-cell leukemia and T-cell lymphoma in adults and may also be involved in certain demyelinating diseases, including tropical spastic paraparesis. Adult T-lymphotropic virus (ATLV) is a strain of this disease that affects primarily adults. A closely related virus is bovine leukemia virus BLV.

HTLV-I
HTLV-I is an abbreviation for the human T-cell lymphotropic virus type 1, also called the Adult T-cell lymphoma virus type 1, a virus that has been seriously implicated in several kinds of diseases including HTLV-I-associated myelopathy, Strongyloides stercoralis hyper-infection, and a virus cancer link for leukemia (see adult T-cell leukemia/lymphoma). Between one in twenty and one in twenty-five infected persons are thought to develop cancer as a result of the virus.

HTLV was discovered in 1977 in Japan. The virus was first isolated by Drs. Bernard Poiesz and Francis Ruscetti and their co-workers in the laboratory of Robert C. Gallo at the NCI. It was the first identified human retrovirus.

Infection with HTLV-I, like infection with other retroviruses, probably occurs for life and can be inferred when antibody against HTLV-1 is detected in the serum.

Prevalence
HTLV-I infection in the United States appears to be about half as prevalent as HIV infection among IV drug users and about one-tenth as prevalent in the population at large. Although little serologic data exist, prevalence of infection is thought to be highest among blacks living in the Southeast. A prevalence rate of 30% has been found among black intravenous drug abusers in New Jersey, and a rate of 49% has been found in a similar group in New Orleans. It is possible that prevalence of infection is increasing in this risk group.

HTLV-I infection in Australia is very high among the Indigenous peoples of central and northern Australia, with a prevalence rate of 10-30%. It is also high among the Inuit of Northern Canada.

Studies of HTLV-I antibody indicate that the virus is endemic in southern Japan, in northeastern Iran , in Peru, in the Pacific coast of Colombia and Ecuador, in the Caribbean, and in Africa.

Transmission
Transmission of HTLV-I is believed to occur from mother to child via breastfeeding; by sexual contact; and through exposure to contaminated blood, either through blood transfusion or sharing of contaminated needles. The importance of the various routes of transmission is believed to vary geographically.


 * In Japan, the geographic clustering of infection and the rarity of unprotected sexual contact suggest that the virus is more dependent on mother-to-child transmission.


 * 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.

Opportunistic infections
Individuals infected with HTLV-1 are at risk for opportunistic infections, diseases not caused by the virus itself, but by alterations in the host's immune functions.

Mechanism
HTLV-1, unlike the distantly related retrovirus HIV, has an immunostimulating effect, which, however, turns out to be immunosuppressive. The virus activates a subset of T-helper cells called Th1 cells. The result is a proliferation of Th1 cells and overproduction of Th1 related cytokines (mainly IFN-gamma and TNF-alpha). Feedback mechanisms of these cytokines cause a suppression of the Th2 lymphocytes and a reduction of Th2 cytokine production (maily IL-4, IL-5, IL-10 and IL-13). The end result is a reduction in the ability of the infected host to mount an adequate immune response to invading organisms that require a predominantly Th2 dependant response (these include parasitic infections and production of mucosal and humoral antibodies).

Examples
In the central Australian Aboriginal population, HTLV-1 is thought to be related to their extremely high rate of death from sepsis.

It is particularly associated with bronchiectasis, a chronic lung condition predisposing to recurrent pneumonia.

It is also associated with chronic infected dermatitis, often superinfected with Staphylococcus aureus and a severe form of Strongyloides stercoralis infection called hyper-infection which may lead to death from polymicrobial sepsis.

HTLV-1 is also associated with adult T cell leukemia/lymphoma, and has been quite well studied in Japan. The time between infection and onset of cancer also varies geographically. It is believed to be about sixty years in Japan, and less than forty years in the Caribbean. The cancer is thought to be due to the pro-oncogenic effect of viral DNA incorporated into host lymphocyte DNA, and chronic stimulation of the lymphocytes at the cytokine level may play a role in development of malignancy. The malignancy ranges from a very indolent and slowly progressive lymphoma to a very aggressive and nearly uniformaly lethal proliferative lymphoma. Treatment varies depending on the type of disease and varies from careful observation to aggressive chemotherapy and antiretroviral agents.

HTLV-1 is also associated with a progressive demyelinating upper motor neurone disease known as HAM/TSP for HTLV-1 associated myelopathy/Tropical Spastic Paparparesis characterized by sensory and motor deficits, particularly of the lower extremities, incontinence and impotence. Less that 2% of infected individuals develop HAM/TSP, but this will vary dramatically from one geographic location to another.

HTLV-II
A virus closely related to HTLV-I, HTLV-II shares approximately 70% genomic homology (structural similarity) with HTLV-I.

It is found predominantly in IV drug users and Native Americans, as well as Caribbean and South American Indian groups.

HTLV-II has not been clearly linked to any disease, but has been associated with several cases of myelopathy/tropical spastic paraparesis (HAM/TSP)- like neurological disease.

HTLV-III and HTLV-IV
The terms "HTLV-III" and "HTLV-IV" have been used to describe recently characterized viruses.

These viruses were discovered in 2005 in rural Cameroon, and were apparently transmitted from monkeys to hunters of monkeys through bites and scratches. HTLV-III is similar to STLV-III (Simian T-lymphotropic virus 3), but HTLV-IV does not resemble any known virus. It is not yet known how much further transmission has occurred among humans, or whether the viruses can cause disease.

The use of these names can cause some confusion, because the name HTLV-III was the former name of HIV in early AIDS literature, but has since fallen out of use. . Also, the name HTLV-IV has been used to describe HIV-2.