Replication, Transcription, and Translation of dsDNA Viruses
Replication of dsDNA viruses is divided into phases (process figure 1). During the early phase, viral DNA enters the nucleus, where several genes are transcribed into messenger RNA. Next, the mRNA transcript moves into the cytoplasm where translation pro duces the viral proteins (enzymes) needed to replicate the viral DNA. This replication usually occurs in the nucleus with the host cell’s own DNA polymerase, though some viruses (herpes, for example) have their own. During the late phase, other viral genes are transcribed and translated into proteins required to form the capsid and other structures. The new viral genomes and capsids are assembled, and the mature viruses are released by budding or cell disintegration.
Process Fig1. General stages in the multiplication of double-stranded DNA viruses. The virus penetrates the host cell and releases DNA, which (1) enters the nucleus and (2) is transcribed by host cell enzymes into mRNA. (3) Viral mRNA leaves the nucleus and is translated into structural proteins; these proteins are transported into the nucleus. (4) Viral DNA is replicated repeatedly in the nucleus. (5) Viral DNA and proteins are assembled into a mature virus in the nucleus. (6) Because it is double stranded, some viral DNA can insert itself into host DNA (latency). Some exceptions to this pattern occur in the poxviruses.
Double-stranded DNA viruses can interact directly with the DNA of their host cell. In some viruses, the viral DNA becomes integrated into the host’s genome by insertion at a particular site on the host genome. Persistence of viral DNA may also lead to the transformation of the host cell into a cancer cell. Several DNA vi ruses, including hepatitis B (HBV), the herpesviruses, and papillomaviruses (warts), are known to be initiators of cancers and are thus termed oncogenic.
Replication, Transcription, and Translation of RNA Viruses
RNA viruses exhibit several differences from DNA viruses. Their genomes are smaller, they enter the host cell already in an RNA form, and the virus cycle occurs entirely in the cytoplasm for most viruses. RNA viruses can have one of the following genetic messages:
1. a positive-strand (+) genome that comes ready to be translated into proteins,
2. a negative-strand (−) genome that must be converted to a positive-strand before translation, and
3. a positive-strand (+) genome that can be converted to DNA or a dsRNA genome.
Positive-Strand Single-Stranded RNA Viruses
The ssRNA of positive-strand viruses such as polio come ready to be translated, so it is immediately translated into a large protein and cleaved into individual functional units. One of these is an RNA polymerase that initiates the replication of the viral strand. Replication of a positive-message strand happens in two steps (process figure2). First, a negative strand is synthesized using the positive strand as a template by the usual base-pairing mechanism. The resultant negative strand becomes a master template that formats the formation of new positive daughter strands. Further translation of the viral genome produces large numbers of structural proteins for final assembly and maturation of the virus.
Process Fig2. Replication of positive-strand, single-stranded RNA viruses. In general, these viruses do not enter the nucleus. (1) Penetration of viral RNA. (2) Because it is positive in message and single-stranded, the RNA can be directly translated on host cell ribosomes into various necessary viral proteins. (3) A negative genome is synthesized against the positive template to produce large numbers of positive genomes for final assembly. (4) The negative template is then used to synthesize a series of positive replicates. (5) RNA strands and proteins assemble into mature viruses released when the cell lyses.
RNA Viruses with Reverse Transcriptase: Retroviruses
A most unusual class of viruses can reverse the order of the flow of genetic information. Thus far in our discussion, all genetic entities have shown the patterns DNA → DNA, DNA → RNA, or RNA → RNA. Retroviruses, including HIV, the cause of AIDS, and HTLV I, a cause of one type of human leukemia, synthesize DNA using their RNA genome as a template. They accomplish this by means of a reverse transcriptase that comes packaged with each virus particle. This enzyme synthesizes a single-stranded DNA against the viral RNA template and then directs the formation of a complementary strand of this ssDNA, resulting in a double strand of viral DNA. The dsDNA strand enters the nucleus, where it can be transcribed by the usual mechanisms into new viral ssRNA and used to assemble new viral particles. When the DNA of some retro viruses becomes inserted into the host’s DNA as a provirus, cells may be transformed and produce tumors. Insertion allows HIV to remain latent in an infected cell for several years.
