Page 360 - Review of Medical Microbiology and Immunology ( PDFDrive )

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CHAPTER 41 Hepatitis Viruses
349
identification and treatment of carriers will reduce
transmission.
Humans are the reservoir for HCV. It is transmitted pri-
marily via blood. At present, injection drug use accounts
for almost all new HCV infections. Transmission from
NON-A, NON-B HEPATITIS VIRUSES
mother to child during birth is another very common
The term “non-A, non-B hepatitis” was coined to describe
the cases of hepatitis for which existing serologic tests had
sion rarely occurs because donated blood containing
ruled out all known viral causes. The term is not often used
antibody to HCV is discarded. Transmission via needle-
because the main cause of non-A, non-B hepatitis, namely, mode of transmission. Transmission via blood transfu-
stick injury occurs, but the risk is lower than for HBV.
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HCV, has been identified. In addition, HDV and HEV have
Sexual transmission is uncommon, and there is no evi-
been described. Cross-protection experiments indicate
dence for transmission across the placenta or during
additional hepatitis viruses exist.
breast feeding.
HCV is the most prevalent blood-borne pathogen in
HEPATITIS C VIRUS (HCV)
data, HCV ranks below HIV and HBV as a blood-borne
pathogen, but it is estimated that HCV is more prevalent.)
Disease
Approximately 4 million people in the United States (1%–
2% of the population) are chronically infected with HCV.
HCV causes hepatitis C.
liver and is transmitted by mosquitoes, there is no evidence
Important Properties
for an insect vector for HCV. Worldwide, it is estimated
HCV is a member of the flavivirus family. It is an enveloped Unlike yellow fever virus, another flavivirus that infects the
that 180 million people are infected with HCV.
virion containing a genome of single-stranded, positive-
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Many infections are asymptomatic, so screening of
polarity RNA. It has no virion polymerase.
high-risk individuals for HCV antibody should be done. In
HCV has at least six genotypes and multiple subgeno-
addition, screening of those who were born between 1945
types based on differences in the genes that encode one of
its two envelope glycoproteins. This genetic variation
infection.
results in a “hypervariable” region in the envelope glyco-
In the United States, about 1% of blood donors have
protein. The genetic variability is due to the high mutation
antibody to HCV. People who share needles when taking
rate in the envelope gene coupled with the absence of a
intravenous drugs are very commonly infected. Commer-
proofreading function in the virion-encoded RNA poly-
cially prepared immune globulin preparations are generally
merase. As a result, multiple subspecies (quasispecies)
very safe, but several instances of the transmission of HCV
often occur in the blood of an infected individual at the
have occurred. This is the only example of an infectious
same time. Genotype 1 causes approximately 75% of infec-
disease transmitted by commercial preparations of immune
tions in the United States.
globulins.
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Summary of Replicative Cycle
The replication of HCV is uncertain because it has not been
grown in cell culture. Other flaviviruses replicate in the
HCV infects hepatocytes primarily, but there is no evidence
cytoplasm and translate their genome RNA into large poly-
for a virus-induced cytopathic effect on the liver cells.
proteins, from which functional viral proteins are cleaved by
Rather, death of the hepatocytes is probably caused by
a virion-encoded protease. This protease is the target of
immune attack by cytotoxic T cells. HCV infection
potent anti-HCV therapy (see treatment section). In addi-
strongly predisposes to hepatocellular carcinoma, but
tion, HCV genome RNA encodes a protein called NS5A that
there is no evidence for an oncogene in the viral genome or
cooperates with the RNA polymerase of the virus to synthe-
size progeny genome RNA’s. The NS5A protein is also the
the cancer cells.
target of potent anti-HCV therapy (see treatment section).
Alcoholism greatly enhances the rate of hepatocellular
The replication of HCV in the liver is enhanced by a for insertion of a copy of the viral genome into the DNA of
carcinoma in HCV-infected individuals. This supports the
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liver-specific micro-RNA called miR-122. This micro-RNA
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idea that the cancer is caused by prolonged liver damage
acts by increasing the synthesis of HCV mRNA. (Micro-
and the consequent rapid growth rate of hepatocytes as the
RNAs are known to enhance cellular mRNA synthesis in
cells attempt to regenerate rather than by a direct onco-
many tissues.) In 2013, a clinical trial of an antisense
nucleotide that bound to and blocked the activity of
observation that patients with cirrhosis of any origin, not
miR-122 showed prolonged reduction in HCV RNA levels
just alcoholic cirrhosis, have an increased risk of hepatocel-
in infected patients.
lular carcinoma.
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