Retroviruses

 The term retro pertains to the reverse transcription of the RNA

genome into DNA.

 These are enveloped viruses with an icosahedral capsid and

two identical strands (said to be “diploid”) of single stranded, linear,
positive-polarity RNA.

 Human T-cell lymphotropic

virus (HTLV) and human

immunodeficiency virus (HIV)

are the two medically important

members of the retrovirus family.

 However, HTLV does not kill T cells, whereas HIV does.

 In fact, HTLV does just the opposite; it causes malignant

transformation that “immortalizes” the infected T cells and allows
them to proliferate in an uncontrolled manner.

 In general, HTLV genes and proteins are similar to those of HIV in

size and function, but the genes differ in base sequence and therefore
the proteins differ in amino acid sequence (and antigenicity).

 The stability of the genes of HTLV is much greater than that of HIV.
As a consequence, HTLV does not show the high degree of variability
of the antigenicity of the envelope proteins that occurs in HIV.
In contrast to other oncogenic retroviruses, HTLV does not possess an
oncogene in its genome and does not integrate its proviral DNA at a
specific site near a cellular oncogene in the T-cell DNA (i.e., it does not
cause insertional mutagenesis). Rather, it is the activation of transcription
of both cellular and viral mRNA synthesis by the Tax protein that
initiates oncogenesis. The tax protein activates the synthesis of IL-2
(which is T-cell growth factor) and of the IL-2 receptor. IL-2 promotes
rapid T-cell growth and eventually malignant transformation of the T
cell.
Human T-cell lymphotropic virus
Transmission:
 HTLV is transmitted primarily by intravenous drug use, sexual contact, or
breast feeding. Transplacental transmission has been rarely documented.

 Transmission by blood transfusion has greatly decreased in the United

States with the advent of screening donated blood for antibodies to HTLV
and discarding those that are positive.

 Transmission by processed blood products, such as immune serum

globulins, has not occurred. Transmission is thought to occur primarily by
the transfer of infected cells rather than free, extracellular virus. For
example, whole blood, but not plasma, is a major source, and infected
lymphocytes in semen are the main source of sexually transmitted virus.
Pathogenesis & Immunity
 HTLV causes two distinct diseases, each with a different type of
pathogenesis.

 One disease is adult T-cell leukemia/lymphoma (ATL) in which

HTLV infection of CD4-positive T lymphocytes induces malignant
transformation.

 HTLV remains latent within the malignant T cells (i.e., HTLV is

typically not produced by the malignant cells).
 The other disease is HTLV-associated myelopathy (HAM), also
known as tropical spastic paraparesis or chronic progressive
myelopathy.

 HAM is a demyelinating disease of the brain and spinal cord,

especially of the motor neurons in the spinal cord.

 HAM is caused either by an autoimmune cross-reaction in which the

immune response against HTLV damages the neurons or by cytotoxic
T cells that kill HTLV-infected neurons.
Clinical findings
 Adult T-cell leukemia/lymphoma (ATL) is characterized by
lymphadenopathy, hepatosplenomegaly, lytic bone lesions, and skin
lesions. These features are caused by proliferating T cells infiltrating
these organs.

 In the blood, the malignant T cells have a distinct “flowershaped”

nucleus. Hypercalcemia due to increased osteoclast activity within the
bone lesions is seen.

 Patients with ATL often have reduced

cell-mediated immunity, and opportunistic

infections with fungi and viruses are common.

 The clinical features of HTLV-associated myelopathy (HAM)
include gait disturbance, weakness of the lower limbs, and low back
pain. Loss of bowel and bladder control may occur. Loss of motor
function is much greater than sensory loss. T cells with a “flower-
shaped” nucleus can be found in the spinal fluid.

 HAM resembles multiple sclerosis except that HAM does not exhibit
the remissions characteristic of multiple sclerosis.

 Both ATL and HAM are relatively rare diseases. The vast
majority of people infected with HTLV develop asymptomatic
infections, usually detected by the presence of antibody.
Treatment & Prevention
 There is no specific antiviral treatment for HTLV infection, and no
antiviral drug will cure latent infections by HTLV.
 ATL is treated with anticancer chemotherapy regimens.
 Antiviral drugs have not been effective in the treatment of HAM.
Corticosteroids and danazol have produced improvement in some
patients.
 There is no vaccine against HTLV.
 Preventive measures include screening donated blood for the presence
of antibodies, using condoms to prevent sexual transmission, and
encouraging women with HTLV antibodies to refrain from breast
feeding.