Primate T-lymphotropic virus

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Primate T-lymphotropic virus
HTLV-1 and HIV-1 EM 8241 lores.jpg
a micrograph showing both Human T-lymphotropic virus 1 and HIV
Scientific classification OOjs UI icon edit-ltr.svg
(unranked): Virus
Realm: Riboviria
Kingdom: Pararnavirae
Phylum: Artverviricota
Class: Revtraviricetes
Order: Ortervirales
Family: Retroviridae
Subfamily: Orthoretrovirinae
Genus: Deltaretrovirus
Groups included

The primate T-lymphotropic viruses (PTLVs) are a group of retroviruses that infect primates, using their lymphocytes to reproduce. The ones that infect humans are known as human T-lymphotropic virus (HTLV), and the ones that infect Old World monkeys are called simian T-lymphotropic viruses (STLVs). PTLVs are named for their ability to cause adult T-cell leukemia/lymphoma, but in the case of HTLV-1 it can also cause a demyelinating disease called tropical spastic paraparesis. [2] On the other hand, newer PTLVs are simply placed into the group by similarity and their connection to human disease remains unclear. [1]

Contents

HTLVs have evolved from STLVs by interspecies transmission. Within each species of PTLV, the HTLV is more similar to its cognate STLV than to the other HTLVs. [1] There are currently three species of PTLVs recognized by the ICTV (P/H/STLV-1, -2, -3), plus two that are reported but unrecognized (HTLV-4, STLV-5). [1] The first known, and still most medically important PTLV is HTLV-1, discovered in 1980. [3]

HTLVs belong to the genus Deltaretrovirus . The only other recognized species in the genus is Bovine leukemia virus , an economically-important cattle pathogen. As its name suggests, this virus causes leukemia in cows. [4]

General virology

Genomic organization of Deltaretrovirues; gag-pro-pol part trimmed off. Pavesi ploscompbio 2013 fig4.png
Genomic organization of Deltaretrovirues; gag-pro-pol part trimmed off.

HTLV-1 is the prototypical PTLV, from which comparisons are drawn for the newly-known types. A retrovirus, PTLV shares the common gag-pro-pol-env set of genes, yet shows great complexity in the unique 3' end. These new proteins provide a great source of new adaptive function: [5]

HTLV-1 has three tandem imperfect 21-base repeats as the long terminal repeat, but other PTLVs only have two. [1]

The lifecycle is common to retroviruses, starting at the envelope glycoprotein (Env) surface subunit (SU) binding to a cellular receptor (in this case GLUT1 and a host of other molecules), [8] and ending with lysis of the cell (in this case, a lymphocyte). [9] The virion is spherical to pleomorphic, about 80-100 nm in diameter. Unusually, the single-stranded RNA genome is present in two copies, forming a dimer speficially packed by parts of the gag protein. [10]

Nomenclatural clarification

The use of "HTLV-3" can cause some confusion, because the name HTLV-III was one of the names for HIV in early AIDS literature, but has since fallen out of use. [11] The name HTLV-IV has also been used to describe HIV-2. [12] A large Canadian study documented this confusion among healthcare workers, where >90% of HTLV tests ordered by physicians were actually intended to be HIV tests. [13]

PTLV-1

PTLV-1 is the medically most important species in the class. Discovered by Robert Gallo and colleagues in 1980, [14] HTLV-1 has been implicated in several kinds of diseases, including tropical spastic paraparesis and as a virus cancer link for adult T-cell leukemia/lymphoma. Between 1 in 20 and 1 in 25 infected people are thought to develop cancer as a result of the virus.[ citation needed ] [15] STLV-1 is oncogenic in Japanese macaques. [16]

HTLV-1 has seven reported subtypes (subtypes A through G). [17] The great majority of infections are caused by the cosmopolitan subtype A. [18] The HTLV-I/STLV-I history might suggest a simian migration from Asia to Africa not much earlier than 19,500–60,000 years ago. [19]

HTLV-2

Discovered in 1982, [20] HTLV-2 has not yet been conclusively linked to any disease. [21] It generally causes no symptoms. It might impact the platelet count, [22] contribute to chronic lung infections, [23] or lead to future cutaneous T-cell lymphoma (CTCL), [24] among a host of other proposals.

HTLV-3

HTLV-3 was discovered in 2005 in rural Cameroon, and were, it is presumed, transmitted from monkeys to hunters of monkeys through bites and scratches. [25] [26] Multiple strains have been identified. [27] A strain has been fully sequenced. [28] [29]

PTLV-3 is about 40% different from PTLV-1 and -2. It occasionally cross-reacts with HTLV-2 tests. It is not yet known how much further transmission has occurred among humans, or whether the virus can cause disease. [1]

HTLV-4

HTLV-4 was discovered at the same site as HTLV-3 in 2005. Even less is known about this virus, as no simian counterpart has ever been found As of 2011. ICTV does not recognize it as a species. The sequence is, however, available. [1]

STLV-5

STLV-5 is a name used for a highly divergent PTLV-1 strain isolated from Macaca arctoides . [1]

Transmission

HTLV-1 and HTLV-2 can be transmitted sexually, [30] [31] by blood to blood contact (e.g. by blood transfusion or sharing needles when using drugs) [32] [33] and via breast feeding. [34]

Epidemiology

Two HTLVs are well established. HTLV-1 and HTLV-2 are both involved in actively spreading epidemics, affecting 15–20 million people worldwide. [35]

HTLV-1 is the more clinically significant of the two: at least 500,000 of the individuals infected with HTLV-1 eventually develop an often rapidly fatal leukemia, while others will develop a debilitative myelopathy, and yet others will experience uveitis, infectious dermatitis, or another inflammatory disorder. HTLV-2 is associated with milder neurologic disorders and chronic pulmonary infections. In the United States, HTLV-1/2 seroprevalence rates among volunteer blood donors average 0.016 percent.[ citation needed ]

No specific illnesses have yet been associated with HTLV-3 and HTLV-4.

Vaccination and treatments

While there is no present licensed vaccine, there are many factors which make a vaccine against HTLV-1 feasible. The virus displays relatively low antigenic variability, natural immunity does occur in humans, and experimental vaccination using envelope antigens has been shown to be successful in animal models. Plasmid DNA vaccines elicit potent and protective immune responses in numerous small-animal models of infectious diseases. However, their immunogenicity in primates appears less potent. In the past two decades a large initiative has been put forth to understand the biological and pathogenic properties of the human T-cell lymphotropic virus type 1 (HTLV-1); this has ultimately led to the development of various experimental vaccination and therapeutic strategies to combat HTLV-1 infection. These strategies include the development of envelope glycoprotein derived B-cell epitopes for the induction of neutralizing antibodies, as well as a strategy to generate a multivalent cytotoxic T-lymphocyte (CTL) response against the HTLV-1 Tax antigen. A vaccine candidate that can elicit or boost anti-gp46 neutralizing antibody response may have a potential for prevention and therapy against HTLV-1 infection. [36]

Potential treatments include prosultiamine, a vitamin B-1 derivative, which has been shown to reduce viral load and symptoms; [37] azacytidine, an anti-metabolite, which has been credited with the cure of a patient in Greece; [38] tenofovir disoproxil (TDF), a reverse-transcriptase inhibitor used for HIV; cepharanthine, an alkaloid from stephania cepharantha hayata; [39] and phosphonated carbocyclic 2'-oxa-3'aza nucleosides (PCOANs). [40] A newer formulation of TDF, called tenofovir alafenamide (TAF), also has promise as a treatment with less toxicity.[ citation needed ]

Related Research Articles

<span class="mw-page-title-main">Retrovirus</span> Family of viruses

A retrovirus is a type of virus that inserts a DNA copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell. After invading a host cell's cytoplasm, the virus uses its own reverse transcriptase enzyme to produce DNA from its RNA genome, the reverse of the usual pattern, thus retro (backward). The new DNA is then incorporated into the host cell genome by an integrase enzyme, at which point the retroviral DNA is referred to as a provirus. The host cell then treats the viral DNA as part of its own genome, transcribing and translating the viral genes along with the cell's own genes, producing the proteins required to assemble new copies of the virus. Many retroviruses cause serious diseases in humans, other mammals, and birds.

<span class="mw-page-title-main">Epstein–Barr virus</span> Virus of the herpes family

The Epstein–Barr virus (EBV), formally called Human gammaherpesvirus 4, is one of the nine known human herpesvirus types in the herpes family, and is one of the most common viruses in humans. EBV is a double-stranded DNA virus. Epstein–Barr virus (EBV) is the first identified oncogenic virus, which establishes permanent infection in humans. EBV causes infectious mononucleosis and is also tightly linked to many malignant diseases. Various vaccine formulations underwent testing in different animals or in humans. However, none of them were able to prevent EBV infection and no vaccine has been approved to date.

<span class="mw-page-title-main">Human T-lymphotropic virus 1</span> Species of virus

Human T-cell lymphotropic virus type 1 or human T-lymphotropic virus (HTLV-I), also called the adult T-cell lymphoma virus type 1, is a retrovirus of the human T-lymphotropic virus (HTLV) family.

Mouse mammary tumor virus (MMTV) is a milk-transmitted retrovirus like the HTL viruses, HI viruses, and BLV. It belongs to the genus Betaretrovirus. MMTV was formerly known as Bittner virus, and previously the "milk factor", referring to the extra-chromosomal vertical transmission of murine breast cancer by adoptive nursing, demonstrated in 1936, by John Joseph Bittner while working at the Jackson Laboratory in Bar Harbor, Maine. Bittner established the theory that a cancerous agent, or "milk factor", could be transmitted by cancerous mothers to young mice from a virus in their mother's milk. The majority of mammary tumors in mice are caused by mouse mammary tumor virus.

<i>Feline leukemia virus</i> Species of virus

Feline leukemia virus (FeLV) is a retrovirus that infects cats. FeLV can be transmitted from infected cats when the transfer of saliva or nasal secretions is involved. If not defeated by the animal's immune system, the virus weakens the cat's immune system, which can lead to diseases which can be lethal. Because FeLV is cat-to-cat contagious, FeLV+ cats should only live with other FeLV+ cats.

<span class="mw-page-title-main">Adult T-cell leukemia/lymphoma</span> Human disease

Adult T-cell leukemia/lymphoma is a rare cancer of the immune system's T-cells caused by human T cell leukemia/lymphotropic virus type 1 (HTLV-1). All ATL cells contain integrated HTLV-1 provirus further supporting that causal role of the virus in the cause of the neoplasm. A small amount of HTLV-1 individuals progress to develop ATL with a long latency period between infection and ATL development. ATL is categorized into 4 subtypes: acute, smoldering, lymphoma-type, chronic. Acute and Lymphoma-type are known to particularly be aggressive with poorer prognosis.

<span class="mw-page-title-main">Oncovirus</span> Viruses that can cause cancer

An oncovirus or oncogenic virus is a virus that can cause cancer. This term originated from studies of acutely transforming retroviruses in the 1950–60s, when the term oncornaviruses was used to denote their RNA virus origin. With the letters RNA removed, it now refers to any virus with a DNA or RNA genome causing cancer and is synonymous with tumor virus or cancer virus. The vast majority of human and animal viruses do not cause cancer, probably because of longstanding co-evolution between the virus and its host. Oncoviruses have been important not only in epidemiology, but also in investigations of cell cycle control mechanisms such as the retinoblastoma protein.

Deltaretrovirus is a genus of the Retroviridae family. It consists of exogenous horizontally transmitted viruses found in several groups of mammals. As of 2023, ICTV lists under this genus the Bovine leukemia virus and three species of primate T-lymphotropic virus.

<span class="mw-page-title-main">Endogenous retrovirus</span> Inherited retrovirus encoded in an organisms genome

Endogenous retroviruses (ERVs) are endogenous viral elements in the genome that closely resemble and can be derived from retroviruses. They are abundant in the genomes of jawed vertebrates, and they comprise up to 5–8% of the human genome.

Following infection with HIV-1, the rate of clinical disease progression varies between individuals. Factors such as host susceptibility, genetics and immune function, health care and co-infections as well as viral genetic variability may affect the rate of progression to the point of needing to take medication in order not to develop AIDS.

The genome and proteins of HIV (human immunodeficiency virus) have been the subject of extensive research since the discovery of the virus in 1983. "In the search for the causative agent, it was initially believed that the virus was a form of the Human T-cell leukemia virus (HTLV), which was known at the time to affect the human immune system and cause certain leukemias. However, researchers at the Pasteur Institute in Paris isolated a previously unknown and genetically distinct retrovirus in patients with AIDS which was later named HIV." Each virion comprises a viral envelope and associated matrix enclosing a capsid, which itself encloses two copies of the single-stranded RNA genome and several enzymes. The discovery of the virus itself occurred two years following the report of the first major cases of AIDS-associated illnesses.

<span class="mw-page-title-main">Viral transformation</span>

Viral transformation is the change in growth, phenotype, or indefinite reproduction of cells caused by the introduction of inheritable material. Through this process, a virus causes harmful transformations of an in vivo cell or cell culture. The term can also be understood as DNA transfection using a viral vector.

Bovine leukemia virus (BLV) is a retrovirus which causes enzootic bovine leukosis in cattle. It is closely related to the human T‑lymphotropic virus type 1 (HTLV-I). BLV may integrate into the genomic DNA of B‑lymphocytes as a DNA intermediate, or exist as unintegrated circular or linear forms. Besides structural and enzymatic genes required for virion production, BLV expresses the Tax protein and microRNAs involved in cell proliferation and oncogenesis. In cattle, most infected animals are asymptomatic; leukemia is rare, but lymphoproliferation is more frequent (30%).

<span class="mw-page-title-main">Human T-lymphotropic virus 2</span> Species of virus

A virus closely related to HTLV-I, human T-lymphotropic virus 2 (HTLV-II) shares approximately 70% genomic homology with HTLV-I. It was discovered by Robert Gallo and colleagues.

<span class="mw-page-title-main">Infectious causes of cancer</span> Pathogens as a cause of cancer

Estimates place the worldwide risk of cancers from infectious causes at 16.1%. Viral infections are risk factors for cervical cancer, 80% of liver cancers, and 15–20% of the other cancers. This proportion varies in different regions of the world from a high of 32.7% in Sub-Saharan Africa to 3.3% in Australia and New Zealand.

<span class="mw-page-title-main">William A. Haseltine</span> American biologist (born 1944)

William A. Haseltine is an American scientist, businessman, author, and philanthropist. He is known for his groundbreaking work on HIV/AIDS and the human genome.

Viral synapse is a molecularly organized cellular junction that is similar in some aspects to immunological synapses. Many viruses including herpes simplex virus (HSV), human immunodeficiency virus (HIV) and human T-lymphotropic virus (HTLV) have been shown to instigate the formation of these junctions between the infected ("donor") and uninfected ("target") cell to allow cell-to-cell transmission. As viral synapses allow the virus to spread directly from cell to cell, they also provide a means by which the virus can escape neutralising antibody.

Feline foamy virus or Feline syncytial virus is a retrovirus and belongs to the family Retroviridae and the subfamily Spumaretrovirinae. It shares the genus Felispumavirus with only Puma feline foamy virus. There has been controversy on whether FeFV is nonpathogenic as the virus is generally asymptomatic in affected cats and does not cause disease. However, some changes in kidney and lung tissue have been observed over time in cats affected with FeFV, which may or may not be directly affiliated. This virus is fairly common and infection rates gradually increase with a cat's age. Study results from antibody examinations and PCR analysis have shown that over 70% of felines over 9 years old were seropositive for Feline foamy virus. Viral infections are similar between male and female domesticated cats whereas in the wild, more feral females cats are affected with FeFV.

Epstein–Barr virus–associated lymphoproliferative diseases are a group of disorders in which one or more types of lymphoid cells, i.e. B cells, T cells, NK cells, and histiocytic-dendritic cells, are infected with the Epstein–Barr virus (EBV). This causes the infected cells to divide excessively, and is associated with the development of various non-cancerous, pre-cancerous, and cancerous lymphoproliferative disorders (LPDs). These LPDs include the well-known disorder occurring during the initial infection with the EBV, infectious mononucleosis, and the large number of subsequent disorders that may occur thereafter. The virus is usually involved in the development and/or progression of these LPDs although in some cases it may be an "innocent" bystander, i.e. present in, but not contributing to, the disease.

William W. Hall is the chair of medical microbiology and professor emeritus at the Centre for Research in Infectious Diseases at University College Dublin.

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