Page 239 - Textbook of Pathology, 6th Edition

223 Neoplasia

CHAPTER 8

Figure 8.26 Integration and replication of RNA virus (retrovirus) in
Figure 8.25 Replication and integration of DNA virus in the host the host cell.
cell. Step 1. The RNA virus invades the host cell. The viral envelope fuses
A, Replication: Step 1. The DNA virus invades the host cell. Step 2. Viral with the plasma membrane of the host cell; viral RNA genome as well as
DNA is incorporated into the host nucleus and T-antigen is expressed reverse transcriptase are released into the cytosol. Step 2. Reverse
immediately after infection. Step 3. Replication of viral DNA occurs and transcriptase acts as template to synthesise single strand of matching
other components of virion are formed. The new virions are assembled viral DNA which is then copied to form complementary DNA resulting in
in the cell nucleus. Step 4. The new virions are released, accompanied double-stranded viral DNA (provirus). Step 3. The provirus is integrated
by host cell lysis. B, Integration : Steps 1 and 2 are similar as in replication. into the host cell genome producing ‘transformed host cell.’ Step 4.
Step 3. Integration of viral genome into the host cell genome occurs Integration of the provirus brings about replication of viral components
which requires essential presence of functional T-antigen. Step 4. A which are then assembled and released by budding.
‘transformed (neoplastic) cell’ is formed.

2. Mode of RNA viral oncogenesis. RNA viruses or v) Viral replication begins after integration of the provirus
retroviruses contain two identical strands of RNA and the into host cell genome. Integration results in transcription of
enzyme, reverse transcriptase (Fig. 8.26): proviral genes or progenes into messenger RNA which then
i) Reverse transcriptase is RNA-dependent DNA synthetase forms components of the virus particle—virion core protein from
that acts as a template to synthesise a single strand of matching gag gene, reverse transcriptase from pol gene, and envelope
viral DNA i.e. reverse of the normal in which DNA is glycoprotein from env gene. The three components of virus
transcribed into messenger RNA. particle are then assembled at the plasma membrane of the
ii) The single strand of viral DNA is then copied by DNA- host cell and the virus particles released by budding off from
dependent DNA synthetase to form another strand of the plasma membrane, thus completing the process of
complementary DNA resulting in double-stranded viral DNA replication.
or provirus. Support to the etiologic role of oncogenic viruses in
iii) The provirus is then integrated into the DNA of the host causation of human cancers is based on the following:
cell genome and may induce mutation and thus transform 1. Epidemiologic data.
the cell into neoplastic cell. 2. Presence of viral DNA in the genome of host target cell.
iv) Retroviruses are replication-competent. The host cells which 3. Demonstration of virally induced transformation of
allow replication of integrated retrovirus are called human target cells in culture.
permissive cells. Non-permissible cells do not permit 4. In vivo demonstration of expressed specific transforming
replication of the integrated retrovirus. viral genes in premalignant and malignant cells.