Blood And Lymph- Htlv By Blue

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Blood and Lymph- Human T-Cell Leukemia Viruses by Blue

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Blood and Lymph- HTLV by Blue

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You associate Flower Cells with?

You associate Hairy Cells with?

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flower cells- HTLV-1

Hairy cells- HTLV-2

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HTLV-1 also is associated with

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HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP)

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Steps in HTLV-1 Oncogenic Transformation: What does the Tax gene do?

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1. encodes tax gene - trans-activator of transcription: viral protein can activate cellular genes (IL-2 and IL-2receptor; autocrine loop).

2. tax also acts as an inhibitor of the expression of tumor suppressor gene p53, and the cyclin dependant kinase (CDK) pathway.

3. RT/Protease inhibitors ineffective for treatment**
-there is no viral replication process going on. you're really just having gene expression that causes proliferation. and has nothing do with virus production. its really just a uncontrolled proliferation. its not a viral replication process...it's a gene expression process. so there are not many good drugs to stop this.

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ATL – 4 groups (following incubation period):

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Acute (50% of cases)
CD4+ cell lymphocytosis (flower cells), skin lesions, lytic bone lesions, hypercalcemia
Opportunistic infections (immunocompromised); Median survival, 6 months

Lymphomatous (25% of cases)
generalized lymphadenopathy, hepatosplenomegaly, no peripheral blood involvement; Median survival, 10 months

Chronic (20% of cases)
Leukocytosis, 10% circulating leukemic cells, other symptoms mild; Median Survival > 2 years

Smoldering (5% of cases)
Normal leukocyte count, 5% leukemic cells. Median survival > 5 years

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HAM/TSP:

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a. Long latency period. Can be concurrent w/ATL.
b. Circulating HTLV-1 infected CD4 T-lymphocytes invade CNS, primarily in spinal cord, at thoracic level. Possible infection of astrocytes. Eventual spread to brain stem.
c. CD8 and cytokine response to infected cells results in inflammation, neuronal destruction, demyelination, and necrotic lesions, leading to:
weakness of all muscle groups in the lower limb (#1),
increased reflexes, Babinski signs,
loss of vibratory and position sense,
incontinence or urinary dysfunction,
constipation, back pain.
Chronic, progressive, won't recover from it.

d. Differentials: MS, encephalomyelitis, progressive multifocal
leukoencephalopathy, Lyme Disease

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Transmission of HTLV-1, 2

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Transmission:
Sexual: (lymphocytes in semen, vaginal secretions);

Mother to Infant: either neonatally (blood) or perinatally (lymphocytes in breast milk);

blood products via transfusion, or shared needles (drug abuse).

Infection via intact, infected cells. All donated blood/blood products are screened for HTLV-1, 2.

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What do you see as an indication that humans acquired this from monkeys?

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STLV 1,2,3

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In words, describe how the infection of HTLV-1 takes place.

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HTLV-1 infects a CD-4 T-cell. It integrates but this is a silent infection because the CD-4 T cells are usually quiescent.

Then via sex, breast feeding, et al, there is a transfer of these T-cells from one person to another, and a graft vs host reaction takes place which activates the infected T-cells to activate and replicate the integrated genome. Also these integrated cells will activate IL-2 and IL-2 receptor which serves as self-stimulation for cell division.

The passed virus will now be dormant in the new host, thanks in part to the Tax Gene which is highly methylated (dampener of transcription). Tax gene also suppresses p53 and CDK which ultimately leads to an adult t cell leukemia.