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A. Typesnavigator

  1. Human T Lymphotropic Virus Type I (HTLV I)
    1. Human Adult T cell leukemia
    2. HTLV-1 Associated Myelopathy (Tropical Spastic Paraparesis)
  2. HTLV II: associated with hairy cell leukemia
  3. Human Immunodeficiency Viruses (HIV-1 and HIV-2)

B. Structurenavigator

  1. All of the retroviruses have gag, pol, env, and tat genes
  2. HIV strains having additional reading frames (for example, 3'orf)
  3. The pol (polymerase) genes codes for three distinct proteins
    1. Self cleaving protease required for processing the functional reverse transcriptase (RT)
    2. RT itself (with associated ribonuclease H activity)
    3. Nuclease involved in integrating viral DNA into the chromosome of the host cell

C. HTLV I [1,2,6]navigator

  1. Virus
    1. T cell tropic, human type C retrovirus
    2. Endemic in southwestern Japan, sub-Saharan Africa, Caribbean, South America
    3. Low level carriage in southeastern USA
    4. Infection associated with antibodies to gag then env, and finally tax proteins
  2. Routes of Transmission
    1. Mother to child (fetal and breast milk)
    2. Sexual contect
    3. Intravenous drugs
    4. Blood transfusion
  3. Proteins
    1. Gag - p19 and p24
    2. Pol - reverse transcriptase (RNA dependent DNA polymerase)
    3. Env - gp21 (small transmembrane) and gp46 (large external envelope glycoprotein)
    4. HTLV1 protease - processes gag gene products
    5. Tax and rex regulatory genes transactivate viral replication and transcription
    6. Tax is primarily responsible for activation of the UTRs
  4. Disease Associations
    1. Adult T cell leukemia in 2-4% of infected patients
    2. Associated with mycosis fungoides / Sezary syndrome (Cutaneous T Cell Lymphoma)
    3. Tropical Spastic Paraparesis / HTLV-1 Associated Myelopathy (HAM/TSP; see below)
    4. Causes Infective Dermatitis in children e Associated with uveitis, dermatitis and pulmonary disease
  5. Adult T Cell Leukemia (ATL)
    1. Multilobulated malignant T lymphocytes, dense chromatin
    2. Patients present with lymphadenopathy, organomegaly, skin lesions, hypercalcemia
    3. Highly resistant to conventional chemotherapy
    4. The malignant T cells display 10,000-35,000 IL-2 receptor alpha chains
    5. Radiolabelled anti-IL2R antibody (yttrium 90-anti-Tac) quite effective [1]
  6. Criteria for Infective Dermatitis [6]
    1. Criteria B-F are Major Criteria (Criteria B,C and F required, as well as D or E)
    2. Eczema of scalp, axillae, and groin, ear area, eylid margins, paranasal skin, and/or neck
    3. Chronic watery nasal discharge without other signs of rhinitis
    4. Chronic relapsing dermatitis with prompt response to antibiotics
    5. Usual onset in early childhood (average 2 years)
    6. HTLV-1 seropositivity
    7. Criteria H-L are minor criteria
    8. Positive cultures of S. aureus or ß-hemolytic strep from skin or anterior nares
    9. Generalized fine papular rash (in most severe cases)
    10. Generalized lymphoadenopathy with dermatopathic lymphadenitis
    11. Hyperimmunoglobulinemia (IgD and IgE)
    12. Raised CD4 and CD8 counts, and increased CD4 to CD8 ratio
    13. Treat with antibiotics
    14. Skin lesions may become less severe over time
  7. No specific therapies yet developed
  8. Vaccine development underway

D. HTLV-1 Associated Myelopathy [3,4,5] navigator

  1. Previously called Tropical Spastic Paraparesis
  2. Chronic progressive myelopathy and atrophy of spinal cord
  3. Subcortical white matter lesions and cerebrospinal fluid changes
  4. Immune mediated mechanisms likely play a role in myelin destruction [5]
    1. Lymphocytes infiltrate leptomeninges and vasculature
    2. Initially, there are equal CD8+ and CD4+ cells
    3. CD8+ cytotoxic T lymphocytes predominate later in disease
    4. Macrophages also play a major role in demyelination
  5. Test patients with idiopathic progressive myelopathy for serum/CSF HTLV-1 Abs
  6. Major competing diagnosis is multiple sclerosis
  7. No current therapy available

E. HTLV IInavigator

  1. Associated with a few cases of Hairy Cell Leukemia
  2. Similar structure to HTLV-1
  3. Association with other human disease is under study

References navigator

  1. Waldmann TA. 1995. JAMA. 273(9):735 abstract
  2. Hollsberg P and Hafler DA. 1993. NEJM. 328:1173 abstract
  3. Osame M, Usuku K, Izumo S, et al. 1986. Lancet. 1:1031 abstract
  4. Gessain A and Gout O. 1992. Ann Internal Med. 117(11):933 abstract
  5. Levin MC, Lehky TJ, Flerlage AN, et al. 1997. NEJM. 336(12):839 abstract
  6. Manns A, Hisada M, La Grenade L. 1999. Lancet. 353(9168):1951 abstract