Supplemental Readings and References
613
Binding sites for host transcription factors;
tat
response elem ent
N u c le o c a p s id -c o re p ro te in s
t
5-LTR
gag
Reverse transcriptase, protease,
integrase, and ribonucléase
t
pot
Strong transcriptional activator
Prom otes infectivity of cell-free virus
W eak transcriptional activator
Inhibits repticaffon o f virus
(negative factor)
Viral coat proteins mediating
CD4 binding and m em brane fusion
FIGURE 26-12
Genome of the human immunodeficiency virus (HIV, or the AIDS virus).
is not possible to prevent or cure infections by retro-
viruses.
The well-characterized retroviruses, HTLV-I, HTLV-II,
and HIV, all exhibit a strong affinity for T cells; HIV specif-
ically recognizes a surface antigen (CD4) on T cells of
the immune system. The organization of the HIV genome
resembles that of the oncogenic RNA viruses described
above but it is considerably more complex. In addition to
the
gag, pol,
and
env
genes and LTR sequences charac-
teristic of all retroviruses, the HIV genome encodes some
additional functions (Figure 26-12). At least four regula-
tory proteins have been provisionally identified encoded
by the
vpr, tat, rev,
and
nef
genes. The envelope protein is
synthesized as a single large polypeptide (gp 160), which
is subsequently cleaved into two structural components.
Most attempts at constructing an effective vaccine utilize
part or all of the envelope proteins as antigens. Since these
proteins do not elicit a strong antibody response by them-
selves, efforts are directed at coupling envelope antigens
with more potent antigens to stimulate antibody response.
The human retroviruses represent a unique class of
infectious agents, and the mechanisms whereby they ulti-
mately result in a variety of diseases are unknown. In com-
parison to infections caused by most other viruses, retro-
viruses are weak antigens. This failure to evoke a strong
immune system response presumably enables them to be-
come established and remain active in cells that they infect.
They rarely produce a strong viremia and consequently
may remain quiescent in infected individuals for years be-
fore clinical symptoms develop. Other yet-to-be-identified
extrinsic or intrinsic factors also may be necessary to ac-
tivate the expression and proliferation of human retro-
viruses. At present, the only protection against retroviral
infections is avoidance of exposure to these agents that are
transmitted primarily through intercourse and exposure to
contaminated blood.
Supplemental Readings and References
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binding attenuation protein, TRAP, bound to RNA.
N a tu re
401,
235
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289,
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L. C. Brody and B. B.Biesecker: Breast cancer susceptibility genes: BRCAI
and BRCA2.
M ed ic in e
77, 208 (1998).
S. B. Cassidy and S. Schwartz: Prader-Willi and Angelman syndromes:
Disorders of genomic imprinting.
M ed ic in e
77, 140 (1998).
G. M. T. Cheetham, D. Jeruzalini, and T. A. Steitz: Structural basis for
initiation of transcription from an RNA polymerase-promoter complex.
N a tu re
399,
80 (1999).
D. Chen, H. Ma, N. Hong, et al.: Regulation of transcription by a protein
methyltransferase.
S c ie n ce
284,
2174 (1999).
P. R. Cook: The organization of replication and transcription.
S cien ce
284,
1790(1999).
Z. Farfel, H. R. Bourne, and T. Iiri: The expanding spectrum of G protein
diseases.
N e w E n g la n d J o u rn a l o f M ed ic in e
340, 1012 (1999).
X. Y. Li, A. Virbasivs, and M. R. Green: Enhancement of TBP binding by
activators and general transcription factors.
N a tu re
399,
605 (1999).
D. A. Haber and E. R. Fearon: The promise of cancer genetics.
T he L a n cet
351,
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E. Heard, P. Clerc, and P. Avner: X-chromosome inactivation in mammals.
A n n u a l R e v ie w o f G en etics
31,
571 (1997).
S. John and J. L. Workman: The facts of chromatin transcription.
S cien ce
282,
1836 (1998).
J. O. Kahn and B. D. Walker: Acute human immunodeficiency virus type I
infection.
N ew E n g la n d J o u rn a l o f M ed icin e
339, 33 (1998).
L. S. Honig and R. N. Rosenberg: Apoptosis and neurologic disease.
A m e rica n J o u rn a l o f M ed ic in e
108,
317 (2000).
P. W. Laird and R. Jaenisch: The role of DNA methylation in cancer genetics
and epigenetics.
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