Page 379 - Review of Medical Microbiology and Immunology ( PDFDrive )

mebooksfree.com
mebooksfree.com
mebooksfree.com

mebooksfree.com
mebooksfree.com
mebooksfree.com
mebooksfree.com mebooksfree.com mebooksfree.com alone is insufficient to cause cancer.) In addition, HTLV-1 mebooksfree.com
mebooksfree.com
mebooksfree.com
PART IV Clinical Virology
368
1. RNA Tumor Viruses
is endemic in some areas of Africa and on several Carib-
Human T-Cell Lymphotropic Virus
bean islands, as shown by the high frequency of antibodies.
The number of people with positive antibody titers in the
There are two human T-cell lymphotropic virus (HTLV)
United States is quite small, except in certain parts of the
isolates so far, HTLV-1 and HTLV-2, both of which are
associated with leukemias and lymphomas. HTLV-1 was
HTLV-2 has 60% genetic homology with HTLV-1. Like
isolated in 1980 from the cells of a patient with a cutaneous
HTLV-1, it is transmitted primarily by blood and semen
T-cell lymphoma. Its RNA and proteins are different from
and infects CD4-positive cells. Routine serologic tests do
those of all other retroviruses. In addition to cancer, HTLV southeastern states.
not distinguish between HTLV-1 and HTLV-2; therefore,
mebooksfree.com mebooksfree.com mebooksfree.com Hepatitis C Virus mebooksfree.com mebooksfree.com
mebooksfree.com
is the cause of tropical spastic paraparesis, an autoimmune
other techniques (e.g., polymerase chain reaction) are
disease in which progressive weakness of the legs occurs.
required.
(Additional information regarding HTLV can be found in
Chapter 39.)
HTLV-1 may cause cancer by a mechanism different
from that of other retroviruses. It has no viral oncogene.
Chronic infection with hepatitis C virus (HCV), like hepa-
Rather, it has two special genes (in addition to the standard
titis B virus (HBV), also predisposes to hepatocellular car-
retroviral genes gag, pol, and env) called tax and rex that
cinoma. HCV is an RNA virus that has no oncogene and
play a role in oncogenesis by regulating mRNA transcrip-
forms no DNA intermediate during replication. It does
tion and translation. The Tax protein has two activities: (1)
it acts on the viral long terminal repeat (LTR) sequences to
predisposing event. (Additional information regarding
stimulate viral mRNA synthesis; and (2) it induces nuclear
HCV can be found in Chapter 41.)
factor-κB (NF-κB), which stimulates the production of cause chronic hepatitis, which seems likely to be the main
interleukin-2 (IL-2) and the IL-2 receptor. The increase in
mebooksfree.com
mebooksfree.com
mebooksfree.com mebooksfree.com mebooksfree.com Human papillomavirus (HPV) is one of the two viruses mebooksfree.com
2. DNA Tumor Viruses
levels of IL-2 and its receptor stimulates the T cells to con-
Human Papillomavirus
tinue growing, thus increasing the likelihood that the cells
will become malignant. The Rex protein determines which
viral mRNAs can exit the nucleus and enter the cytoplasm
definitely known to cause tumors in humans. Papillomas
to be translated.
(warts) are benign but can progress to form carcinomas,
HTLV-1 is not an endogenous virus (i.e., proviral DNA
especially in an immunocompromised person. HPV pri-
corresponding to its RNA genome is not found in normal
marily infects keratinizing or mucosal squamous epithe-
human cell DNA). It is an exogenously acquired virus
lium. (Additional information regarding HPV can be
because its proviral DNA is found only in the DNA of the
malignant lymphoma cells. It infects CD4-positive T cells
Papillomaviruses are DNA nucleocapsid viruses with
preferentially and will induce malignant transformation in
double-stranded, circular, supercoiled DNA and an icosa-
these cells in vitro. Some (but not all) patients with T-cell found in Chapter 38.)
hedral nucleocapsid. Carcinogenesis by HPV involves two
lymphomas have antibodies against the virus, indicating
mebooksfree.com
mebooksfree.com mebooksfree.com mebooksfree.com mal cells. In cancer cells, the viral DNA is integrated into mebooksfree.com
mebooksfree.com
proteins encoded by HPV genes E6 and E7 that interfere
that it may not be the cause of all T-cell lymphomas. Anti-
with the activity of the proteins encoded by two tumor sup-
bodies against the virus are not found in the general popu-
pressor genes, p53 and Rb (retinoblastoma), found in nor-
lation, indicating that infection is not widespread.
Transmission occurs primarily by breast feeding, by
the cellular DNA, and the E6 and E7 proteins are
sexual contact, and by exchange of contaminated blood
produced.
(e.g., in transfusions and intravenous drug users). In the
There are at least 100 different types of HPV, many of
United States, blood for transfusions is screened for anti-
which cause distinct clinical entities. For example, HPV-1
bodies to HTLV-1 and HTLV-2 and discarded if positive. In
through HPV-4 cause plantar warts on the soles of the feet,
recent years, HTLV-1 and HTLV-2 were found in equal
whereas HPV-6 and HPV-11 cause anogenital warts (con-
frequency in donated blood. Serologic tests for HTLV do
not cross-react with human immunodeficiency virus (HIV).
types of HPV, especially types 16 and 18, are implicated as
At about the same time that HTLV-1 was found, a simi-
the cause of carcinoma of the cervix, penis, and anus.
lar virus was isolated from malignant T cells in Japan. In dylomata acuminata) and laryngeal papillomas. Certain
mebooksfree.com mebooksfree.com mebooksfree.com from the cells of an East African individual with Burkitt’s mebooksfree.com
mebooksfree.com
mebooksfree.com
that country, a clustering of cases in the rural areas of the
Epstein–Barr Virus
west coast of Kyushu was found. Antibodies in the sera of
leukemic individuals and in the sera of 25% of the normal
Epstein–Barr virus (EBV) is a herpesvirus that was isolated
population of Kyushu react with the Japanese isolate and
with HTLV-1. (Only a small fraction of infected individu-
lymphoma. EBV, the cause of infectious mononucleosis,
als contract leukemia, indicating that HTLV infection
transforms B lymphocytes in culture and causes
mebooksfree.com mebooksfree.com mebooksfree.com mebooksfree.com mebooksfree.com mebooksfree.com