General characteristics and virion structure
The family Retroviridae unites a unique group of viruses comprising about 150 different species. Members of this family are spherical particles with a diameter varying between 80 and 130 nanometers. The virion has a complex multilevel organization. Externally, it is covered by a supercapsid, which is an outer lipid envelope. Beneath this envelope lies the nucleocapsid core, characterized by an icosahedral type of symmetry.
The most important defining feature of all family members is the presence of a specific enzyme — reverse transcriptase, also called RNA-dependent DNA polymerase. This enzyme is physically closely associated with the viral genetic material. The viral genome itself has a unique structure: it is diploid and represents a complex consisting of two absolutely identical subunits of single-stranded positive RNA (+RNA).
Organization of the genetic apparatus
The organization of the retrovirus genome is strictly ordered. The genome contains both structural envelope proteins and enzymes, as well as specific regulatory elements. In addition, the presence of approximately 30 different oncogenes (oncoantigens) in the genome is known.
Structural genes are arranged in a specific order (from the 5' end to the 3' end):
- gag: gene encoding group-specific capsid antigens (specifically, viral proteins p27–p30).
- pol: gene responsible for the synthesis of polymerase (revertase).
- env: gene encoding proteins of the surface spikes of the viral envelope.
At the edges, the structural genes are bounded by long terminal repeats — LTR (Long Terminal Repeats). These regulatory sequences perform a crucial function: they control the processes of transcription and viral integration. Structurally, LTR elements include binding sites for cellular polymerases and tRNA (acting as a primer), a transactivator gene functioning as a transcription enhancer, and repeating regions at the edges necessary for the successful insertion of viral DNA into the host cell chromosome.
Life cycle and reproduction
Retroviruses have strict cultivation requirements: they do not multiply at all in chicken embryos. For their successful growth in laboratory conditions, sensitive cell cultures are used or susceptible animals are infected.
The initial stages of the replicative cycle begin with the penetration of the virion into the target cell via endocytosis. Once inside, the virus undergoes deproteinization: the nucleocapsid emerges from the vacuole, which leads to the activation of revertase.
The subsequent process of reverse transcription proceeds in three obligatory stages with the direct participation of revertase:
- A minus-strand DNA is synthesized on the template of the original viral RNA. Cellular tRNA is used as a primer for this process.
- Enzymatic cleavage (degradation) of the original template viral RNA occurs.
- A plus-strand DNA is built on the template of the newly synthesized first DNA strand.
The result of these reactions is the formation of a linear double-stranded DNA molecule. Due to the presence of LTR regulatory structures, this molecule circularizes. At the final stage of replication, the synthesized circular viral DNA integrates into the host cell genome, forming a provirus. Further transcription of the genes of the integrated provirus is carried out by the cellular enzyme, RNA polymerase II.
Classification and clinical significance
The family Retroviridae is characterized by wide diversity and high pathogenicity. It is known that about 150 species of these viruses are capable of inducing tumor development in animals. In modern taxonomy, the family is divided into two major subfamilies:
- Orthoretrovirinae: includes 6 genera (Alpharetrovirus, Betaretrovirus, Gammaretrovirus, Deltaretrovirus, Epsilonretrovirus, Lentivirus).
- Spumaretrovirinae: represented by a single genus Spumavirus.
Among the vast number of retroviruses, four main species are recognized as clinically significant for humans. This group includes human immunodeficiency viruses (HIV-1 and HIV-2, which are classic representatives of the family) and human T-cell leukemia viruses (HTLV-1 and HTLV-2).
The HTLV group of viruses (Human T-lymphotropic virus) belongs to the genus Deltaretrovirus. Their main target in the human body is CD4+ T-lymphocytes. Oncogenicity has currently been reliably proven for HTLV-1 and HTLV-2 species.
Briefly: answers to topical questions
What enzymes, besides reverse transcriptase, make up the retrovirus virion?
In addition to reverse transcriptase (revertase), the retrovirus virion contains several other enzymes necessary for replication. According to the genetic structure, the pol gene encodes the following core enzyme complex:
- Integrase — an enzyme for inserting viral DNA into the host cell genome.
- Protease — an enzyme for processing viral proteins.
- RNase — an enzyme involved in the replication of the viral genome.
What receptors and coreceptors does HIV use to enter the target cell?
To enter the target cell, HIV uses the main CD4 receptor and the chemokine coreceptors CCR5 and CXCR4. The process includes the following stages:
- Main receptor — CD4, to which the surface viral glycoprotein gp120 initially binds.
- Coreceptors — chemokine receptors CCR5 and/or CXCR4, additional binding to which is a critical step for the virus to penetrate inside the cell.
In the early stages of infection, the virus exhibits tropism predominantly for macrophage CCR5 receptors, and subsequently shifts to binding CXCR4 on the surface of T cells.
What specific diseases does the HTLV-1 virus cause in humans?
Sources indicate that HTLV-1 belongs to human T-cell leukemia viruses and has proven oncogenicity. Its target is CD4+ T-lymphocytes.
By what mechanism do new retrovirus virions exit the infected cell?
The exit of new retrovirus virions from the infected cell occurs via budding. During the release process, the viral particle captures a patch of the host cell's plasma membrane, from which the outer double-layer lipoprotein envelope (supercapsid) of the virion is formed. In the human immunodeficiency virus, this process is facilitated by the action of a specific Vpu peptide (the product of the vpu gene), which blocks premature binding of viral proteins inside the cell and ensures successful budding of new virions.
Which surface and transmembrane glycoproteins are encoded by the env gene in HIV?
The env gene in the human immunodeficiency virus encodes structural proteins of the outer envelope (glycoprotein spikes). Depending on the virus type, this gene encodes the following glycoproteins:
| Virus type | Surface glycoprotein | Transmembrane glycoprotein |
|---|---|---|
| HIV-1 | gp120 | gp41 |
| HIV-2 | gp140 / gp105 | gp36 |
In HIV-1, the surface glycoprotein gp120 protrudes outward and is responsible for initial receptor binding, while the transmembrane glycoprotein gp41 is embedded in the lipoprotein envelope and mediates membrane fusion.
Class and exam questions
What is the main feature of retroviruses?
They are reverse-transcribing viruses. The presence of the reverse transcriptase enzyme allows them to synthesize DNA from a viral RNA template for subsequent integration into the genome.
In what form does the viral genome integrate into the cell chromosome?
Integration occurs in the form of a provirus. After reverse transcription, the double-stranded viral DNA circularizes and integrates into the host genome.
What type of genome is characteristic of the Retroviruses family?
The genome is diploid. It is represented by a complex of two absolutely identical subunits of single-stranded plus-RNA (+RNA).
Which body cells are infected by the HTLV virus?
The main target of human T-cell leukemia viruses (HTLV-1 and HTLV-2) is CD4+ T-lymphocytes.
What else to study on this topic
- The role of retroviral oncogenes in host cell transformation
- Functions of capsid proteins p27–p30
- Features of the pathogenesis of HIV-1 and HIV-2 viruses
- Mechanism of oncogenicity of HTLV-1 and HTLV-2 viruses
- Transcription transactivator and its role in LTR elements
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