Retrovirus, also known as reverse transcriptionViruses, belonging to a class of RNA viruses, their genetic information is not stored inDeoxyribonucleic acid(DNA), but stored inRibonucleic acid(RNA).The retroviral genome is a diploid, two identical single stranded positive strand RNAs with long terminal repeat (LTR) at both ends, containing strong promoters and enhancers, which play an important role in the transcriptional regulation of viral DNA.The virus core containsReverse transcriptaseAnd integrase.Different from other RNA viruses, retroviral RNA does not self replicate. After entering the host cell, RNA synthesizes double stranded DNA through reverse transcriptase, and the double stranded DNA is integrated into the chromosome DNA of the host cell by integrase to form a provirus, which establishes lifelong infection and can be transmitted to the offspring cells along with the host cell division.
The integration of retroviral DNA is the replication of virusesRNAThe necessary stage of.The site where the retroviral DNA genome is randomly integrated into the host chromosome.Each infected cell usually has 1~10 copiesPrevirusCopy.DNA Insertion of Retrovirushost cellChromosomes lose 2 bp at the left end of U3 of 5'LTR and 2 bp at the right end of U5 of 3'LTR, while 4-6 bpRepeating sequence。Only when the infected cells are incell divisionDuring this period, the retroviral DNA genome can contact the genetic material of the host cell.Therefore, retroviruses can only replicate in dividing cells.
The discovery of their reverse transcriptase enriches the "central law" of genetics, and their special reproduction mode also enables people to acquire more knowledge about gene transcription, genome replication and integration.In addition, retroviruses can be used as vectors for gene transfer in mammalian cells, which will provide a broad application prospect for gene therapy of human molecular diseases.[1]
(1) All retroviruses have a structural feature, that is, large spherical particles with a size of 80~100 nm.There are intact protruding outer membranes.
(2) The chemical composition of retroviral particles is almost the same, with RNA accounting for 2% and protein accounting for 60%~70%, of which 5%~7% are complex glycoproteins, lipids 30%~40% and carbohydrates 1%~2%.
(3) Enzymes play a special role in retroviral encoded proteins.The most characteristic enzyme of retrovirus is reverse transcriptase.Its presence in cells is evidence of retroviral infection.The main function of reverse transcriptase is to ensure that RNA templates from different sources can synthesize DNA.
(4) Oncogenes play a major role in viral transformation in cells that allow viruses to reproduce.The gene sequence of Rous sarcoma virus: 5 '- LT R – gag – pol – env – src – LTR - 3' represents the structural feature of the retroviral genome. The main structural feature is that the two ends of the gene have the same terminal repeat sequence (LTR), which includes the promoter and enhancer of the virus.When virus binds to cell, LTR can improve the activity of adjacent virus and cell genes.Gag is a protein gene encoding the complete structure of viral particles, pol is a reverse transcriptase gene, also known as polymerase gene, env is the outer membrane protein gene of viral particles, also known as envelope gene, src is the transformation gene of corresponding cells, and this substance is neither a component of viral particles nor a structural protein.[3]
characteristic
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1) The virus is spherical, with a diameter of 100~120 nm, and the capsid is 20 faceted, with stereo symmetryenvelope；
2) The genome is diploid (the only genome is non haploid virus), and the two are the same+ssRNA；
4) Replication passes through the DNA intermediate and integrates with the chromosome of the host cell (the only virus that actively integrates);
5) It has gag, pol, env coding genes and long terminal repeat sequence LTR;
6) Mature virusBuddingMode release;
7) It has a very high mutation rate and is prone to drug resistance. Once infected, it will carry the virus for life.For the time being, there is no effective vaccine that can be prevented, and there is no way to completely eliminate the virus;
8) The incubation period of the virus is very long, usually up to several years or even decades.
Infected
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Whether retroviral infection can be realized depends on cell characteristics, cell division phase and the existence of virus related receptors.The sensitivity of virus is determined by cell genes.Only when many conditions are met can tumor factors infect cells.First, the virus is adsorbed on the cell surface.In this process, cell receptors and membrane proteins play a leading role, and cells will not be infected by viruses without corresponding receptors.In sensitive cells, the adsorbed virus passes through the cell membrane, removes its own protein membrane, and activates the function of enzymes in virus particles.Then, viral RNA is mixed with the nucleus.Finally, with the participation of reverse transcriptase, double stranded circular DNA is synthesized on the template of viral RNA, which is called previrus.
Proviruses are intrinsic to retroviruses.The intermediate phase of DNA is necessary for the proliferation of the virus itself.All single RNAs with infectious ability synthesize their own RNA through double stranded DNA.There is no double stranded viral RNA in retrovirus infected cells.The replication path of retroviral RNA is: viral RNA → DNA → proviral → RNA.The final product of DNA previrus synthesis is RNA DNA hybrid molecule.
When the provirus transits from cytoplasm to nucleus, in addition to the dominant filamentous form of the provirus, there is also a circular structure with single or double stranded ends overlapping. The circular structure is the precursor of the provirus. Before the formation of the circular structure, under the influence of enzymes, the circular molecules of the provirus expand at the double stranded end repeat sequence and connect to certain parts of the host cell chromosome,There are many parts of the cell genome that can be linked to the provirus.Proviruses that survive in the DNA of cells are kept in cells for a long time and passed down from generation to generation.At first, they were subordinate to the regulation mechanism of cells.Therefore, their state depends largely on the state of cells.The expression of previrus is that virus information is transcribed by cellular enzymes.As a result of transformation, the formed viral RNA is transferred from the nucleus to the cytoplasm.
The synthesis of viral protein begins on the ribosome.At this time, the cellular enzyme system is involved in the formation of viral membrane glycoprotein, which is accompanied by changes in the cell membrane.The formation of virus particles is carried out with the help of virus proteins and virus devices. After the particles are formed, they are released to the outside of the cell. In this way, effective infection is completed.
The cell has the nature of tumor, which does not depend on the existence of virus particles in the cell, but the special substance of the virus, namely the transformation protein, plays a role.The proviral DNA provides the regulation device of the virus and can exist in the infected cells for a long time. Without the formation of such substances, the cells will not be damaged and they will not show their own existence.When the pre DNA virus is in the latent state, all the necessary materials it carries are to become active under appropriate conditions, transmit protein synthesis information, and put on the shell necessary for the virus particle to mature, so that the cells can undergo fundamental changes and turn normal cells into tumor cells.[3]
spread
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The transmission of retrovirus in nature can be divided into horizontal transmission and vertical transmission.Horizontal transmission is spread through personal contact, such as the transmission of feline leukemia virus.Vertical transmission refers to the transmission from the previous generation to the next generation. Pathogens are latent in the body for a long time without showing any characteristics or causing any symptoms of disease.Only under the influence of special conditions can the virus become active. For the host, it may induce the occurrence and development of tumors, even death.This transmission is often successfully transmitted to offspring through breast milk, mammalian sex cells or bird eggs.[3]
