Viruses Whose Life Cycle Uses Reverse
Transcriptase
hybrid. This activity is essential for the production of a
INTRODUCTION
dsDNA copy of the viral RNA by RT. The destruction of
the RNA template makes the process of reverse transcrip-
Two families of animal viruses utilize reverse transcriptase
tion fundamentally different from other mechanisms used
(RT) in the replication of their genome, the Retroviridae and
for transcription or copying of nucleic acids, in which the
the Hepadnaviridae. Two floating genera of plant viruses
template remains intact.
also use RT; their life cycles are more similar to the hepadna-
An essential feature of the infection of cells by retrovi-
viruses than to the retroviruses. The hepadnaviruses and the
ruses is that the dsDNA copy of the genome is integrated
plant viruses are sometimes called pararetroviruses because
into the host chromosome, where it is called a provirus. Only
their life cycle resembles that of the retroviruses.
integrated DNA is stably and efficiently transcribed by the
For the viruses that use RT, the genetic information in
host machinery. Thus, integration is required for productive
the genome alternates between being present in RNA and
infection. During infection by hepadnaviruses, in contrast,
present in DNA. RT, which is encoded in the viral genome,
the viral DNA does not integrate. Instead, it is maintained
converts the RNA genome of retroviruses, or an RNA copy
in the nucleus as a nonreplicating episome. In contrast to
of the DNA genome of hepadnaviruses, into double-stranded
retroviruses, hepadnaviral episomal DNA is stably and effi-
(ds) DNA. In the nucleus of the infected cell, cellular RNA
ciently transcribed by the host machinery.
polymerase transcribes the DNA genome of hepadnaviruses,
The retroviruses have been intensively studied for years
or the DNA copy of the retrovirus genome, to produce the
because researchers discovered early that avian retroviruses
RNA to be reverse transcribed. The retroviruses package this
have the ability to induce leukemias and sarcomas in chick-
RNA in the virion and are allied to retrotransposons that form
ens. The study of these viruses led to the discovery of cel-
a prominent feature of eukaryotic genomes. The hepadnavi-
lular oncogenes, of RT, and of mechanisms that regulate
ruses and the plant viruses reverse transcribe the RNA into
cycling of the animal cell, and several Nobel Prizes have
DNA during packaging, so that the virion contains DNA.
been awarded for work with the avian retroviruses (Chapter
Thus, the replication of the genome of retroviruses can be
described as RNA→DNA→RNA, whereas the replication of
1). Although clearly important for our understanding of biol-
the genome of hepadnaviruses can be described as DNA→
ogy, for many years after their discovery retroviruses were
RNA→DNA. Although the two families differ in the timing
in some ways biological curiosities because no human dis-
ease was known to be associated with retroviral infection.
of when reverse transcription takes place in their life cycles,
This changed with the discovery of human T-cell leukemia
this difference may not represent a fundamental distinction
viruses, now known as primate T-lymphotropic viruses
between them. Recent studies have shown that one genus of
(PTLV), which cause leukemia in humans, and with the
retroviruses, the spumaviruses, packages DNA in the virion.
appearance of human immunodeficiency virus (HIV), which
It is an interesting feature of reverse transcription that the
causes acquired immunodeficiency syndrome (AIDS).
RNA template is destroyed in the process of conversion to
These viruses have dramatically altered our understanding
DNA. RT has associated with it an RNase H activity, which
of the disease-causing potential of retroviruses.
specifically degrades the RNA strand of a DNARNA
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