Page 339 - Review of Medical Microbiology and Immunology ( PDFDrive )

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PART IV Clinical Virology
328
also appears to cause these diseases, but the association is
Viral mRNA is made by host cell RNA polymerase, and
less clearly documented. (All information in this section
refers to HTLV-1 unless otherwise stated.)
transcription is upregulated by Tax protein, as mentioned
earlier. The Rex protein controls the synthesis of the gag/pol
Important Properties
mRNA, the env mRNA, and their subsequent transport to
the cytoplasm, where they are translated into structural viral
HTLV and HIV are the two medically important members
of the retrovirus family. Both are enveloped viruses with
genome RNA is also synthesized and transported to the
reverse transcriptase in the virion and two copies of a sin-
cytoplasm. The virion nucleocapsid is assembled in the
gle-stranded, positive-polarity RNA genome. However, proteins. Full-length RNA destined to become progeny
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cytoplasm, and budding occurs at the outer cell membrane.
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HTLV does not kill T cells, whereas HIV does. In fact,
Cleavage of precursor polypeptides into functional struc-
HTLV does just the opposite; it causes malignant transfor-
tural proteins is mediated by the virus-encoded protease.
mation that “immortalizes” the infected T cells and allows
them to proliferate in an uncontrolled manner.
The genes in the HTLV genome whose functions have
HTLV is transmitted primarily by intravenous drug use,
been clearly identified are the three structural genes com-
sexual contact, or breast feeding. Transplacental trans-
mon to all retroviruses, namely, gag, pol, and env, plus two
mission has been rarely documented. Transmission by
regulatory genes, tax and rex. In general, HTLV genes and
blood transfusion has greatly decreased in the United
proteins are similar to those of HIV in size and function,
but the genes differ in base sequence, and therefore the
antibodies to HTLV and discarding those that are posi-
proteins differ in amino acid sequence (and antigenicity).
tive. Transmission by processed blood products, such as
For example, p24 is the major nucleocapsid protein in both
immune serum globulins, has not occurred. Transmis-
HTLV and HIV, but they differ antigenically. The virions of States with the advent of screening donated blood for
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sion is thought to occur primarily by the transfer of
both HTLV and HIV contain a reverse transcriptase, inte-
infected cells rather than free, extracellular virus. For
grase, and protease. The envelope proteins of HTLV are
example, whole blood, but not plasma, is a major source,
gp46 and gp21, whereas those of HIV are gp120 and gp41.
The proteins encoded by the tax and rex genes play the
of sexually transmitted virus.
same functional roles as those encoded by the HIV regula-
HTLV infection is endemic in certain geographic areas,
tory genes, tat and rev. The Tax protein is a transcriptional
namely, the Caribbean region including southern Florida,
activator, and the Rex protein governs the processing of
eastern South America, western Africa, and southern
viral mRNA and its export from the nucleus to the cyto-
Japan. The rate of seropositive adults is as high as 20% in
plasm. Tax protein is required for malignant transforma-
tion of T cells.
because infected individuals migrate from these areas of
In contrast to other oncogenic retroviruses, such as
endemic infection. At least half the people in the United
Rous sarcoma virus in chickens (see page 363), HTLV does
States who are infected with HTLV are infected with
not possess an oncogene in its genome and does not inte- some of these areas, but infection can occur anywhere
HTLV-2, usually acquired via intravenous drug use.
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grate its proviral DNA at a specific site near a cellular onco-
gene in the T-cell DNA (i.e., it does not cause insertional
Pathogenesis & Immunity
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
type of pathogenesis. One disease is adult T-cell leuke-
synthesis of IL-2 (which is T-cell growth factor) and of the
mia/lymphoma (ATL) in which HTLV infection of CD4-
IL-2 receptor. IL-2 promotes rapid T-cell growth and even-
positive T lymphocytes induces malignant transformation.
tually malignant transformation of the T cell.
As described earlier, HTLV-encoded Tax protein
The stability of the genes of HTLV is much greater than
enhances synthesis of IL-2 (T-cell growth factor) and
that of HIV. As a consequence, HTLV does not show the
IL-2 receptor, which initiates the uncontrolled growth
high degree of variability of the antigenicity of the envelope
characteristic of a cancer cell. All the malignant T cells
proteins that occurs in HIV.
contain the same integrated proviral DNA, indicating
that the malignancy is monoclonal (i.e., it arose from a
Summary of Replicative Cycle
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single HTLV-infected cell). HTLV remains latent within
The replication of HTLV is thought to follow a typical retro-
the malignant T cells (i.e., HTLV is typically not pro-
viral cycle, but specific information has been difficult to
duced by the malignant cells).
The other disease is HTLV-associated myelopathy
obtain because the virus grows poorly in cell culture. HTLV
primarily infects CD4-positive T lymphocytes. The cellular
chronic progressive myelopathy. HAM is a demyelinating
receptor for the virus is unknown. Within the cytoplasm,
reverse transcriptase synthesizes a DNA copy of the genome,
disease of the brain and spinal cord, especially of the motor
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