In this article we will discuss about:- 1. Meaning of Retroviruses 2. Structural Organization of Retroviruses 3. Genomic Organization 4. Replication.
Meaning of Retroviruses:
Retrovirus is a virus containing RNA genome that replicates through a DNA intermediate. The term “retro” means “backward” and the name “retrovirus” is derived from the fact that these viruses transfer information backward from RNA to DNA, a mechanism opposite to most of the viruses that transfer information forward from DNA to RNA.
The interesting backward-information-transfer mechanism of these viruses is earned out by an RNA-dependent DNA polymerase enzyme called reverse transcriptase (RT).
The use of reverse transcriptase is not the property of only retroviruses; viruses like hepatitis B (a human virus) and cauliflower mosaic (a plant virus) also use reverse transcriptase in their replication but, unlike retroviruses, they contain DNA as genetic material.
A number of retroviruses such as human immunodeficiency virus (HIV), leukemia virus, human foamy virus human T-cell lymphotrophic virus, simian immunodeficiency virus, visna virus, etc. are now known. Retroviruses are credited to be the first viruses shown to cause cancer. They have been studied more extensively for their carcinogenic properties, and because of this property they are also known as oncornaviruses.
Most of the retroviruses infect vertebrates including fish, reptiles, birds, mammals, etc. Of the most studied retroviruses are rous sarcoma virus (RSV), leukemia viruses of chicken and mice, and human immunodeficiency virus (HIV) that causes acquired immunodeficiency syndrome (AIDS) in humans.
Structural Organization of Retroviruses:
Retroviruses are enveloped icosahedral viruses measuring about 100-120 nm. The envelop encloses the virion. On the outer surface of virion several spikes are present which contain glycoproteins. There are several proteins in the viral coat; typically seven are internal proteins, four of which are structural and three enzymatic.
The enzymes occurring in the virion are reverse transcriptase, DNA endonuclease (integrase), and a protease. The virion also contains specific cellular tRNA molecules. In addition to all these, there is centrally placed genome that is represented by RNA.
Genomic Organization of Retroviruses:
The genomic organization of the retrovirus is unique. Its genome consists of two identical linear ssRNA molecules of plus (+) complementarity. Although there are differences in genes in different retroviruses, all retroviruses possess the following genes that are arranged in the same order.
These genes are:
(1) Gag gene, which encodes structural proteins,
(2) Pol genes that encode reverse transcriptase and DNA endonuclease(integrase), and
(3) Env gene that encodes envelop proteins.
Some retroviruses (e.g., Rous sarcoma virus) possess a fourth gene which is considered to be involved in cellular transformation and cancer. A genetic map of a typical retrovirus genome is shown in Fig. 14.9.
Replication of Retroviruses:
The overall process of replication of a retrovirus can be summarized in the following steps:
(1) Adsorption, penetration, and un-coating of the virion,
(2) Reverse transcription,
(3) Integration,
(4) Transcription,
(5) Assembly of nucleocapsid, and
(6) Release of viruses.
1. Adsorption, penetration, and un-coating of the virion:
Adsorption to the host cell surface is the first step in the retrovirus replication cycle. It takes place with the random collision of the virion with a plasma membrane receptor site. The receptors are specific, for convenience, the retrovirus HIV uses CD4 and CXCR-4 (fusion) or the CCR5 (CC-CKR-5) receptor. However, retroviruses penetrate the plasma membrane and enter the host cell shortly after adsorption.
The envelops of these viruses fuse directly with the host cell plasma membrane; fusion may involve special envelop fusion glycoproteins that bind to plasma membrane proteins. During fusion the membrane lipids are rearranged, the adjacent halves of the contacting membranes are merged, and a proteinaceous fusion pore develops. Finally the nucleocapsid enters the host cell cytoplasm where un-coating is completed.
2. Reverse transcription:
Reverse transcription, the conversion of RNA into DNA with the help of enzyme reverse transcriptase (RNA-dependent DNA polymerase) present in the virion, is the step that follows the entry of virus into the host cell. Like all DNA polymerases, reverse transcriptase needs a primer for DNA synthesis. The primer for retrovirus reverse transcription is a specific cellular transfer RNA (tRNA), which is packaged in the virion during its assembly in the previous host cell.
The conversion of RNA into DNA takes place in two steps. First, reverse transcriptase copies the +RNA to form a RNA-DNA hybrid. Then the ribonuclease H component (RNase H) of reverse transcriptase degrades the +RNA strand to leave -DNA. After synthesizing -DNA, the reverse transcriptase copies this strand to produce a dsDNA.
The dsDNA enters the host nucleus along with the integrase protein, and is integrated into the host DNA. The dsDNA of virus contains long terminal repeats (LTRs) at its both ends; the LTRs contain strong promoters of transcription and are also involved in the integration process.
3. Integration:
Integration of the viral dsDNA into the host DNA is analogous to the integration of phage DNA into a bacterial chromosome to bring lysogenic state. Viral DNA can integrate anywhere in the host DNA. When integrated, the viral DNA is called provirus (or proviral DNA). The latter is a stable genetic element that reproduces simultaneously with host DNA, and can remain this way indefinitely.
4. Transcription:
Promoters present in the right LTR are activated and direct provirus (proviral DNA) transcription by a cellular RNA polymerase into new viral RNA and mRNA. New viral RNAs are encapsidated into virus particles as viral genome, whereas mRNA are translated into virus coat (capsid) proteins.
5. Assembly of nucleocapsid:
When virus coat proteins are accumulated sufficiently, the assembly of nucleocapsid takes place. Encapsulation of new viral RNAs capsids leads to the formation of mature nucleocapsids, which move to the plasma membrane for final assembly into the enveloped virus particles.
6. Release of viruses:
Retroviruses are enveloped viruses and they are released from the host cell in a manner different from those of naked viruses that are released most often by host cell lysis. The formation of envelops and the release of enveloped viruses are usually concurrent processes, and the host cell may continue the release of enveloped viruses for some time.
Virus-encoded proteins are incorporated into the plasma membrane and then the nucleocapsid is simultaneously released by budding through the plasma membrane; the envelop is formed during the process of membrane budding. In this way, the released retroviruses escape from the infected host cell without destroying it and infect neighbouring host cells.
A summarized diagrammatic representation of the overall replication process of a retrovirus is given in Fig. 14.10: 