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A Microbial Biorealm page on the genus HTLV2


Viruses; Retro-transcribing viruses; Retroviridae; Orthoretrovirinae; Deltaretrovirus; Primate T-lymphotrophic virus 2 (1).

Description and significance

HTLV-2 (Human T-Cell Lymphotrophic Virus Type II or Human T-Cell Leukemia Virus Type II) has been implicated in several neurological diseases, but its high rate of co-infection with the AIDS virus is a confound to these observations (see the Ecology section). Though newly discovered, HTLV-2 has already been utilized as a model system of the retrovirus, due its homology to the HTLV-1 virus. This is especially relevant to the study of the evolution of viruses, as the genome of HTLV-2 suggests an alternate path of evolution from the HTLV-1 virus. This has provided invaluable phylogenetic information. Its high rate of co-infection with other auto-immune diseases has illuminated the need for more accurate diagnostic techniques, as this virus is not easily detectable by current methods. Disorders possibly caused by the HTLV-2 virus are similar toother auto-immune disorders (such as MS, Lyme disease, and lupus) which are not easily diagnosed and whose antibodies are not easily detected. Its prominence in drug users, specifically in North America and Europe, has also demonstrated the need for awareness campaigns concerning the dangers of sharing needles. Ultimately, the shortcomings in HTLV-2 research illustrates a lack of appropriate technology and unbiased research in the field of pathogenic retroviruses. (4, 6, 7)

Genome structure

HTLV-2’s genome is completely sequenced. It has a linear chromosome of single stranded RNA with seven genes, which include HTLV2gp1-6 and HTLV2gs1. It consists of 8,952 nucleotides and has a GC content of 53%. It shows approximately 60% homology to the human T-cell leukemia virus type I. This homology makes it an important research model of deltaretroviruses. Its genomic structure is as follows: LTR-gag-protease-pol-env-X-LTR. The protease gene encodes a protease that can cleave the precursor Gag protein encoded by gag. The pol gene encodes for 982 amino acids. The env gene encodes for 486 amino acids. The X region of the gene is likely responsible for the replication of the virus. The high ratio of synonomous to nonsynomous changes to HTLV-2s genome from HTLV-1’s genome suggests that ability of this virus to produce certain amino acids was not significantly changed. (5,11,12)

Cell structure, metabolism & life cycle

(also see Genome section) As a retrovirus, the structure of HTLV-2 is mainly provided by its matrix protein. HTLV-2's matrix protein is structurally homologous to that of the HIV-1 virus, suggesting that this structure is evolutionarily conserved. While its specific life cycle is not well-characterized, it does appear to be similar to the general life cycle of a retrovirus. The primary structural proteins are the polypeptides matrix (MA), capsid (CA) and nucleocapsid (NC). HTLV-2s Rex protein is responsible for the expression of proteins within the virus. The expression of these proteins mediates the death of the host cell after infection by HTLV-2. The envelope of retroviruses is anchored to a shell primarily composed of matrix proteins. Unlike their genomic sequence which is relatively similar, the matrix proteins of HTLV-2 and HTLV-1 only show approximately 10% homology. This structural difference may mediate the viral and pathogenic differences of the two strains. This difference is supported by the discovery that the gene products of HTLV-1 and HTLV-2's ORF differ greatly (p28 of HTLV-2 cannot effectively modulate transcription as p30 of HTLV-1 can, respectively). Nevertheless, without p28 HTLV-2 has a reduced ability to infect other cells. As further described in the Ecology section, HTLV-2 infects host cells as a classic retrovirus does: it attaches itself to a host cell receptor, produces the reverse transcriptase enzyme, and produces DNA within the host cell from its own RNA. (9, 10)

Ecology (including pathogenesis)

HTLV-2 was first discovered in 1982 in a patient with hairy-cell leukemia, a rare type of leukemia that most often affects men but can affect women. Prior to this study, it was thought that retroviruses could not infect humans as they had been found in many animal models but never in humans. Subsequent studies were unable to demonstrate that HTLV-2 was the cause of the leukemia, but it has been implicated in certain neurological disorders and increased bacterial infections in the bloodstreams of AIDS patients. In a recent study examining the incidence of AIDS patients co-infected with HTLV-2, patients infected with both viruses were more likely to develop peripheral neuropathy than those only infected with one of the viruses. While other studies have demonstrated similar increased risk of certain neurological disorders with HTLV-2 infection, these studies are confounded with the presence of other viruses. (The rate of co-infection also suggests that the weakened immune response of AIDS patients is allows the HTLV-2 virus to infect the individual, as it rarely presents itself in patients by itself.) These suggested neurological disorders caused by HTLV-2 include HAM/TSP, multiple system atrophy (MSA), and ataxia. HAM/TSP most often results in muscle stiffness and weakness and increased frequency of urination. The symptoms of MSA are very similar to Parkinson's disease. Ataxia refers to a loss of muscle coordination. As a retrovirus, HTLV-2 bind to specific receptors on the host cell and replicate by releasing reverse transcriptase to create DNA from its single stranded RNA genome. HTLV-2 alters gene expression that increases the production of lymphocytes and ultimately changes the structure of its most prominent target, the CD8+ lymphocyte. It is not understand how the virus is able to change the structure of the cell. The HTLV-2 virus has multiple modes of transmission, related to its ability to stay attached to its host cell even after replication. Some studies state that is it not passed in utero while others suggest that it does, but it is clear that it can pass from mother to child through breast milk. Up to 25% of children with mothers who have the disease and breastfeed will contract the virus. It is sexually transmitted and is more easily transmitted from a male to a female than a female to a male. It is also commonly transmitted through needle sharing; this is the prominent mode of transmission in North America, Europe, South America, and Asia. It is endemic to certain Amerindian tribes, such as the Guahibo Indians of Venezuela. It is also endemic to the Bakola pygmy tribe of Africa, as compared to local African tribes. The endemism if the virus is likely due to its vertical transmission through breast feeding. Because the overall incidence of HTLV-2 infection is so rare, and because it effects very specific subsets of the world population, the pathogenesis of HTLV-2 is unclear. Recent research has demonstrated that the protein Tax stimulates two interleukins (IL-14 and IL-2), which increases T-cell growth and may be responsible for the change in cell structure. This causes leukogenesis, which may explain why the HTLV-2 virus was first discovered in a leukemia patient though the virus could not be isolated from any other patients with the same type of leukemia. The tax protein differs among different subtypes (a, b, c) of the virus, but it is not known if this is related to pathogenesis. It is probable that the pathogenesis of HTLV-2 is similar to that of HTLV-1, in which the increase in T-cell proliferation leads to T-cell killing by the body's immune system which releases damaging cytokines and lymphokines. This response is typical of an auto-immune disease. (2, 3, 5, 6, 7, 8, 13)

Interesting feature

A recent study demonstrated that both HTLV-1 and HTLV-2 are able to mediate glucose metabolism by binding to the glucose receptor Glut-1. Infected cells showed reduced lactate production and consumption and the cultures in which they grow became more acidic. Glucose consumption of infected cells was decreased by up to 95%. The binding of HTLV to GLUT-1 receptors by demonstrated by these findings, as well as the similarity in structure to the previously unidentified HTLV receptor. In addition, overexpression of GLUT-1 receptors caused a paralell increase in HTLV binding to the cells. Lastly, when glucose transport is inhibited by cytochalasin B, HTLV binding significantly decreased. Further research is needed to determine if this implicated modification of glucose metabolism by HTLV infection is involved in the pathogenesis of HTLV. (14)


1. NCBI Taxonomy Browser. Human T-lymphotrophic virus 2.

2. Leon-Ponte, Matilde, Noya, Oscar, Bianco, Nicolas, De Perz, Gloria Echeverria. "Highly endemic Human T-Lymphotrophic Virus Type II (HTLV-II) Infection in a Venezuelan Guahibo Amerindian Group" J. Acquir Immune Defic Syndr. 1996. Volume 13(3):281-286.

3. Boxus M, Twizere JC, Legros S, Dewulf JF, Kettmann R, Willems L. "The HTLV-1 Tax interactome." Retrovirology. Volume 5(76). Dooneief G, Marlink R, Bell K, et al. "Neurologic consequences of HTLV-II infection in injection-drug users." Neurology.1996. Volume 46(6):1556-1560.

4. Araujo, A. Hall, William W. "Human T-Lymphotrophic Virus Type II and Neurological Disease." 2004. Annals of Neurology.Volume 56(1).

5. Lairmore, Michael D., Montgomery, Andy. "Isolation and Confirmation of Human T-Cell Leukemia Virus Type 2 from Peripheral Blood Mononuclear Cells." Methods Mol Biol. 2005. Volume 304:113-123.

6. Szczypinska, E.M. "Human T-Cell Lymphotrophic Viruses." Medscape Reference. 2009.

7. Zehender, G., Colastante C, Santambrogio S, De Maddalena C, Massetto B, Cavilli B, Jacchetti G, Fasan M, Adorni F, Osio M, Moroni M, Galli M. "Increased risk of developing peripheral neuropathy in patients co-infected with HIV-1 and HTLV-2." 2002. J Acquir Immune Defic Syndr. Volume 31(4): 440-447.

8. Mauclere P, Afonso PV, Meertens L, Plancoulaine S, Calattini S, Froment A, Van Beveren M, de The G, Quintana-Murci L, Mahieux R, Gessain A. “HTLV-2B strains, similar to those found in several Amerindian tribes, are endemic in African Bakola Pygmies. Journal of Infectious Diseases. 2011. Volume 203(9):1316-1323.

9. Christensen, Allyson M., Massiah, Michael A., Turner, Brian G, Sundquist, Wesley I, Summers, Michael F. "Three-Dimensional Structure of the HTLV-II Matrix Protein and Comparative Analysis of Matrix Proteins from the Different Classes of Pathogenic Human Retroviruses." J. Mol. Biol. 1996. Volume 264: 1117-1131.

10. Yamamoto B, Li M, Kesic M, Younis I, Lairmore MD, Green PL. "Human T-cell leukemia virus type 2 post-transcriptional control protein p28 is required for viral infectivity and persistence in vivo." Retrovirology. 2008. Volume 12(5).

11. NCBI Genome. "Human T-lymphotropic virus 2, complete genome."

12. Shimotohno K, Takahashi Y, Shimizu N, Gojobori T, Golde DW, Chen IS, Miwa M, Sugimura T. “Complete nucleotide sequence of an infectious clone of human T-cell leukemia virus type II: an open reading frame for the protease gene.” 1985. Volume 82 (10): 3101-3105.

13. Kalyanaraman, V.S., Sarngadharan, M.G., Robert-Guroff, Marjorie, Miyoshi, Isao, Blayney, Douglas, Golde, David, Gallo, Robert C. “A New Subtype of Human-T-Cell Leukemia Virus (HTLV-II) Associated with a T-Cell Variant of Hairy Cell Leukemia. Science. 1982. Volume 218 (4572): 571-573.

14. Manel, Nicolas, Kim, Felix J, Kinet, Sandrina, Taylor, Naomi, Sitbon, Marc, Battini, Jean-Luc. "The Ubiquitous Glucose Transporter GLUT-1 Is a Receptor for HTLV." Cell. 2003. Volume 114:449-459.