Human T-lymphotropic virus
Encyclopedia
Human T-cell Lymphotropic Virus Type 1 (HTLV-I), 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
.
Other neurologic findings that may be found in HTLV include:
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 users 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, in Japan
, northeastern Iran
, Peru
, the Pacific coast
of Colombia
and Ecuador
, the Caribbean
, and in Africa
.
or sharing of contaminated needles. The importance of the various routes of transmission is believed to vary geographically.
, a glucose transporter, on target cells.
s, diseases not caused by the virus itself, but by alterations in the host's immune functions.
, has an immunostimulating effect which actually becomes 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-γ and TNF-α). Feedback mechanisms of these cytokines cause a suppression of the Th2 lymphocytes and a reduction of Th2 cytokine production (mainly 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 dependent response (these include parasitic infections and production of mucosal and humoral antibodies).
.
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-infestation which may lead to death from polymicrobial sepsis.
Adult T cell lymphoma is a common complication of HLTV infection, and requires aggressive chemotherapy, typically R-CHOP. Other treatments for ATL in HLTV infected patients include interferon alpha, zidovudine
with interferon alpha, and CHOP with arsenic trioxide. Treatments for HLTV myelopathy are even more limited, and focus mainly on symptomatic therapy. Therapies studied include corticosteroids, plasmapherisis, cyclophosphamide
, and interferon
, which may produce a temporary symptomatic improvement in myelopathy symptoms.Valproic acid
has been studied to determine if it might slow the progression of HLTV 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 HLTV-1. It is important to monitor for opportunistic infections such as cytomegalovirus
, histoplasmosis, scabies, pneumocystis pneumonia, and staphylococcal infection
s in HLTV patients. 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 HLTV-1 disease, with varied results. One case report describes a HLTV-1 infected woman who developed chronic refractory eczema, corneal injury, and adult T cell leukemia. She was subsequently treated with allogenic stem cell transplantion, and had complete resolution of symptoms. One year posttransplant, she has had no recurrence of any symptoms, and furthermore has had a decrease in her proviral load.
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
that has been seriously implicated in several kinds of diseases including HTLV-I-associated myelopathy, Strongyloides stercoralis
Strongyloides stercoralis
Strongyloides stercoralis, also known as the threadworm, is the scientific name of a human parasitic roundworm causing the disease of strongyloidiasis....
hyper-infection, and a virus cancer link for leukemia
Leukemia
Leukemia or leukaemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases...
(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
Robert Gallo
Robert Charles Gallo is an American biomedical researcher. He is best known for his role in the discovery of the Human Immunodeficiency Virus , the infectious agent responsible for the Acquired Immune Deficiency Syndrome , and he has been a major contributor to subsequent HIV research.Gallo is the...
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
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
.
Signs and symptoms of HTLV myelopathy
Signs and symptoms of HTLV myelopathy include:- Motor and sensory changes in the extremities
- SpasticSpasticThe word spastic is used differently depending on location which has led to some controversy and misunderstanding. Derived via Latin from the Greek spastikos , the word originally referred to a change in muscles affected by the medical condition spasticity, which is seen in spastic diplegia and...
gait in combination with weakness of the lower limbs - ClonusClonusClonus is a series of involuntary muscular contractions and relaxations. Clonus is a sign of certain neurological conditions, and is particularly associated with upper motor neuron lesions such as in stroke, multiple sclerosis, spinal cord damage and hepatic encephalopathy...
- Bladder dysfunction and bladder cancer
Other neurologic findings that may be found in HTLV include:
- Mild cognitive deficits
- Erectile dysfunction
Prevalence
HTLV-I infection in the United StatesUnited States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
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 users in New Jersey
New Jersey
New Jersey is a state in the Northeastern and Middle Atlantic regions of the United States. , its population was 8,791,894. It is bordered on the north and east by the state of New York, on the southeast and south by the Atlantic Ocean, on the west by Pennsylvania and on the southwest by Delaware...
, 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
Inuit
The Inuit are a group of culturally similar indigenous peoples inhabiting the Arctic regions of Canada , Denmark , Russia and the United States . Inuit means “the people” in the Inuktitut language...
of Northern Canada, in Japan
Japan
Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...
, northeastern Iran
Iran
Iran , officially the Islamic Republic of Iran , is a country in Southern and Western Asia. The name "Iran" has been in use natively since the Sassanian era and came into use internationally in 1935, before which the country was known to the Western world as Persia...
, Peru
Peru
Peru , officially the Republic of Peru , is a country in western South America. It is bordered on the north by Ecuador and Colombia, on the east by Brazil, on the southeast by Bolivia, on the south by Chile, and on the west by the Pacific Ocean....
, the Pacific coast
Pacific Coast
A country's Pacific coast is the part of its coast bordering the Pacific Ocean.-The Americas:Countries on the western side of the Americas have a Pacific coast as their western border.* Geography of Canada* Geography of Chile* Geography of Colombia...
of Colombia
Colombia
Colombia, officially the Republic of Colombia , is a unitary constitutional republic comprising thirty-two departments. The country is located in northwestern South America, bordered to the east by Venezuela and Brazil; to the south by Ecuador and Peru; to the north by the Caribbean Sea; to the...
and Ecuador
Ecuador
Ecuador , officially the Republic of Ecuador is a representative democratic republic in South America, bordered by Colombia on the north, Peru on the east and south, and by the Pacific Ocean to the west. It is one of only two countries in South America, along with Chile, that do not have a border...
, the Caribbean
Caribbean
The Caribbean is a crescent-shaped group of islands more than 2,000 miles long separating the Gulf of Mexico and the Caribbean Sea, to the west and south, from the Atlantic Ocean, to the east and north...
, and in Africa
Africa
Africa is the world's second largest and second most populous continent, after Asia. At about 30.2 million km² including adjacent islands, it covers 6% of the Earth's total surface area and 20.4% of the total land area...
.
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 transfusionBlood transfusion
Blood transfusion is the process of receiving blood products into one's circulation intravenously. Transfusions are used in a variety of medical conditions to replace lost components of the blood...
or sharing of contaminated needles. The importance of the various routes of transmission is believed to vary geographically.
- In Japan, the geographic clustering of infections 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.
Tropism
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 GLUT1GLUT1
Glucose transporter 1 , also known as solute carrier family 2, facilitated glucose transporter member 1 is a protein that in humans is encoded by the SLC2A1 gene...
, a glucose transporter, on target cells.
Opportunistic infections
Individuals infected with HTLV-1 are at risk for opportunistic infectionOpportunistic infection
An opportunistic infection is an infection caused by pathogens, particularly opportunistic pathogens—those that take advantage of certain situations—such as bacterial, viral, fungal or protozoan infections that usually do not cause disease in a healthy host, one with a healthy immune system...
s, diseases not caused by the virus itself, but by alterations in the host's immune functions.
Mechanism
HTLV-1, unlike the distantly related retrovirus HIVHIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
, has an immunostimulating effect which actually becomes immunosuppressive. The virus activates a subset of T-helper cells
T helper cell
T helper cells are a sub-group of lymphocytes, a type of white blood cell, that play an important role in the immune system, particularly in the adaptive immune system. These cells have no cytotoxic or phagocytic activity; they cannot kill infected host cells or pathogens. Rather, they help other...
called Th1
T helper cell
T helper cells are a sub-group of lymphocytes, a type of white blood cell, that play an important role in the immune system, particularly in the adaptive immune system. These cells have no cytotoxic or phagocytic activity; they cannot kill infected host cells or pathogens. Rather, they help other...
cells. The result is a proliferation of Th1 cells and overproduction of Th1 related cytokines (mainly IFN-γ and TNF-α). Feedback mechanisms of these cytokines cause a suppression of the Th2 lymphocytes and a reduction of Th2 cytokine production (mainly 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 dependent 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 sepsisSepsis
Sepsis is a potentially deadly medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection. The body may develop this inflammatory response by the immune system to microbes in the blood, urine, lungs, skin, or other tissues...
.
It is particularly associated with bronchiectasis
Bronchiectasis
Bronchiectasis is a disease state defined by localized, irreversible dilation of part of the bronchial tree caused by destruction of the muscle and elastic tissue. It is classified as an obstructive lung disease, along with emphysema, bronchitis, asthma, and cystic fibrosis...
, a chronic lung condition predisposing to recurrent pneumonia
Pneumonia
Pneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...
.
It is also associated with chronic infected dermatitis
Dermatitis
-Etymology:Dermatitis derives from Greek derma "skin" + -itis "inflammation" and genetic disorder.-Terminology:There are several different types of dermatitis. The different kinds usually have in common an allergic reaction to specific allergens. The term may describe eczema, which is also called...
, often superinfected with Staphylococcus aureus
Staphylococcus aureus
Staphylococcus aureus is a facultative anaerobic Gram-positive coccal bacterium. It is frequently found as part of the normal skin flora on the skin and nasal passages. It is estimated that 20% of the human population are long-term carriers of S. aureus. S. aureus is the most common species of...
and a severe form of Strongyloides stercoralis
Strongyloides stercoralis
Strongyloides stercoralis, also known as the threadworm, is the scientific name of a human parasitic roundworm causing the disease of strongyloidiasis....
infection called hyper-infestation which may lead to death from polymicrobial sepsis.
Leukemia
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 uniformly lethal proliferative lymphoma.Tropical spastic paraparesis
HTLV-1 is also associated with a progressive demyelinating upper motor neurone disease known as HAM/TSP for HTLV-1 associated myelopathy/Tropical Spastic Paraparesis characterized by sensory and motor deficits, particularly of the lower extremities, incontinence and impotence. Less than 2% of infected individuals develop HAM/TSP, but this will vary dramatically from one geographic location to another.Treatment
Treatment for opportunistic infections varies depending on the type of disease and varies from careful observation to aggressive chemotherapy and antiretroviral agents.Adult T cell lymphoma is a common complication of HLTV infection, and requires aggressive chemotherapy, typically R-CHOP. Other treatments for ATL in HLTV infected patients include interferon alpha, zidovudine
Zidovudine
Zidovudine or azidothymidine is a nucleoside analog reverse-transcriptase inhibitor , a type of antiretroviral drug used for the treatment of HIV/AIDS. It is an analog of thymidine....
with interferon alpha, and CHOP with arsenic trioxide. Treatments for HLTV myelopathy are even more limited, and focus mainly on symptomatic therapy. Therapies studied include corticosteroids, plasmapherisis, cyclophosphamide
Cyclophosphamide
Cyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group....
, and interferon
Interferon
Interferons are proteins made and released by host cells in response to the presence of pathogens—such as viruses, bacteria, or parasites—or tumor cells. They allow communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.IFNs belong to...
, which may produce a temporary symptomatic improvement in myelopathy symptoms.Valproic acid
Valproic acid
Valproic acid is a chemical compound that has found clinical use as an anticonvulsant and mood-stabilizing drug, primarily in the treatment of epilepsy, bipolar disorder, and, less commonly, major depression. It is also used to treat migraine headaches and schizophrenia...
has been studied to determine if it might slow the progression of HLTV 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
Zidovudine
Zidovudine or azidothymidine is a nucleoside analog reverse-transcriptase inhibitor , a type of antiretroviral drug used for the treatment of HIV/AIDS. It is an analog of thymidine....
showed a major decrease in the viral load of baboons infected with HLTV-1. It is important to monitor for opportunistic infections such as cytomegalovirus
Cytomegalovirus
Cytomegalovirus is a viral genus of the viral group known as Herpesviridae or herpesviruses. It is typically abbreviated as CMV: The species that infects humans is commonly known as human CMV or human herpesvirus-5 , and is the most studied of all cytomegaloviruses...
, histoplasmosis, scabies, pneumocystis pneumonia, and staphylococcal infection
Staphylococcal infection
Staphylococcus is a genus of Gram-positive bacteria which includes several species that can cause a wide variety of infections in humans and other animals through either toxin production or invasion....
s in HLTV patients. 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 HLTV-1 disease, with varied results. One case report describes a HLTV-1 infected woman who developed chronic refractory eczema, corneal injury, and adult T cell leukemia. She was subsequently treated with allogenic stem cell transplantion, and had complete resolution of symptoms. One year posttransplant, she has had no recurrence of any symptoms, and furthermore has had a decrease in her proviral load.