Retroviruses are a unique class of viruses distinguished by their ability to convert their genetic material, RNA, into DNA. This process, known as reverse transcription, is the opposite of the typical flow of genetic information. The discovery of reverse transcriptase challenged the central dogma of molecular biology, which stated genetic information flows only from DNA to RNA to protein. This unique replication strategy allows retroviruses to integrate their genetic information into the host cell’s genome, leading to persistent infections and having significant implications in biology and medicine, including their association with diseases like AIDS and certain cancers.
General Organization of a Retrovirus
A retrovirus exhibits a layered architecture with distinct components arranged concentrically. The outermost layer is a lipid envelope, acquired from the host cell during viral budding. Beneath this envelope lies a protein shell called the matrix, which provides structural support. Further inward, a conical or roughly spherical capsid encases the viral genetic material and associated enzymes. This arrangement protects viral components and facilitates entry and replication within host cells.
The Viral Envelope and Its Proteins
The retroviral envelope forms the outermost boundary of the virion. This lipid bilayer is derived from the plasma membrane of the infected host cell as new viral particles exit. Embedded within this host-derived membrane are specific viral proteins known as glycoproteins. These glycoproteins exist as complexes, composed of two subunits: a surface unit (SU) and a transmembrane unit (TM).
The surface unit (SU) is exposed on the exterior of the virion and binds to specific receptor molecules on target host cells. This specific attachment determines which cell types a retrovirus can infect. The transmembrane unit (TM) anchors the SU protein to the viral envelope and plays a role in the fusion of the viral envelope with the host cell membrane. This fusion allows the inner components of the retrovirus to enter the host cell’s cytoplasm.
The Inner Core: Capsid, Matrix, and Genetic Material
Beneath the viral envelope lies the matrix (MA) layer, a protein shell. This matrix layer serves as a bridge, connecting the outer envelope to the internal components of the virion. It maintains the structural integrity of the retrovirus particle, ensuring the envelope remains associated with the inner core. The matrix also participates in the assembly of new viral particles within the host cell.
Enclosed by the matrix layer is the capsid (CA) shell, a protective container for the retrovirus’s genetic material and enzymes. The capsid’s shape can vary among retroviruses, often appearing as a cone-like structure in some, such as HIV, while others may exhibit a more spherical or icosahedral symmetry. This robust protein shell shields the viral RNA genome from degradation within the host cell.
Within the capsid are two identical copies of the retroviral genetic material: single-stranded RNA. These RNA molecules are positive-sense, meaning they can serve as messenger RNA within the host cell. Along with the RNA, the virion also packages specific transfer RNA (tRNA) molecules derived from the host cell. These host tRNAs are incorporated into the virion during assembly and serve as primers for the reverse transcription process.
Key Enzymes Within the Virion
Packaged within the retroviral core, alongside the genetic material, are several enzymes necessary for the virus’s replication cycle. Primary among these is reverse transcriptase (RT), an enzyme that catalyzes the conversion of the retroviral RNA genome into a double-stranded DNA copy. This enzyme possesses multiple activities, including RNA-dependent DNA polymerase activity, ribonuclease H (RNase H) activity to degrade the RNA template, and DNA-dependent DNA polymerase activity to synthesize the second DNA strand.
Another enzyme is integrase (IN), which is responsible for inserting the newly synthesized viral DNA into the host cell’s chromosomal DNA. This integration step permanently modifies the host genome, allowing viral genes to be transcribed by the host cell’s machinery. Without integrase, the viral DNA would not establish a stable presence within the host cell, preventing new viral particle production.
Protease (PR) is also an enzyme, playing a role in the maturation of new virions. During viral assembly, retroviral proteins are synthesized as large precursor polyproteins. Protease cleaves these polyproteins into their individual, functional protein components. This enzymatic processing is required for the proper formation of the mature, infectious retrovirus particle.