General Characteristics and Virion Structure
The family Retroviridae comprises a unique group of viruses containing approximately 150 different species. Members of this family are spherical particles with a diameter varying between 80 and 130 nanometers. The virion possesses a complex, multi-layered 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 defining feature of all family members is the presence of a specific enzyme—reverse transcriptase, also known as 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 consists of a complex of two absolutely identical subunits of single-stranded positive-sense RNA (+RNA).
Organization of the Genetic Apparatus
The organization of the retroviral genome is strictly ordered. The genome contains structural envelope proteins, enzymes, and specific regulatory elements. In addition, approximately 30 different oncogenes (oncoantigens) are known to exist within the genome.
Structural genes are arranged in a specific sequence (from the 5'-end to the 3'-end):
- gag: encodes group-specific capsid antigens (specifically, viral proteins p27–p30).
- pol: encodes the polymerase (reverse transcriptase) and associated enzymes.
- env: encodes the envelope surface spike glycoproteins.
- tax/rex (in complex retroviruses): regulatory proteins.
At the flanks, structural genes are bounded by Long Terminal Repeats (LTRs). These regulatory sequences perform a critical function: they control viral transcription and integration. Structurally, LTR elements include binding sites for cellular polymerases and tRNA (serving as a primer), a transactivator gene that acts as a transcription enhancer, and repeated sequences at the ends necessary for successful integration of the viral DNA into the host cell chromosome.
Life Cycle and Replication
Retroviruses have strict requirements for cultivation conditions: they do not replicate in embryonated chicken eggs. For successful in vitro propagation, sensitive cell cultures or susceptible animals are used.
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 uncoating: the nucleocapsid is released from the vacuole, leading to the activation of reverse transcriptase.
Subsequent reverse transcription proceeds in three obligatory steps with the direct participation of reverse transcriptase:
- A minus-strand DNA is synthesized using the original viral RNA as a template. 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 synthesized using the newly synthesized first DNA strand as a template.
The outcome of these reactions is the formation of a linear double-stranded DNA molecule. Due to the presence of LTR regulatory structures, this molecule circularizes. In the final replication step, the synthesized circular viral DNA integrates into the host cell genome, forming a provirus. Subsequent transcription of the integrated provirus genes is carried out by the host cellular enzyme, RNA polymerase II.
Classification and Clinical Significance
The family Retroviridae is characterized by wide diversity and high pathogenicity. Approximately 150 species of these viruses are capable of inducing tumors 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 primary species are recognized as clinically significant for humans. This group includes the human immunodeficiency viruses (HIV-1 and HIV-2, which are classic members of the family) and the human T-lymphotropic viruses (HTLV-1 and HTLV-2).
The HTLV group (Human T-lymphotropic virus) belongs to the genus Deltaretrovirus. Their primary target in the human body is CD4+ T lymphocytes. Oncogenicity has been reliably proven for HTLV-1 and HTLV-2.