Life cycle of adenovirus comprises of several steps like attachment, internalization, Uncoating, replication, biosynthesis, assembly and release of virus progeny. After releasing from the host cell, it infects new cells and can cause infections either for a short term or long term. Adenovirus mainly causes four kinds of infection like a productive, abortive, latent and oncogenic infection. The life cycle of adenovirus involves three major stages like infection, replication and multiplication phases.
At the time of infection, a virus gets entered into the host cell via a cell-mediated receptor and through the process of “Endocytosis”.
The replication occurs in the nucleus of the host cell where it produces copies of viral progenies by taking the host cell machinery.
The multiplication phase involves two phases, namely the early and late phase, which produces early and late gene products respectively. The early and late gene products help in the regulation and synthesis of structural components of virion.
After multiplication, the virus particles get assembled and release out of the cell by causing cell death or through budding. Adenovirus can enter into the host cell via respiratory droplets, close contact and faecal-oral route.
After getting entry into the host cell, a virus first attacks the mucoepithelial cells and can cause direct cell damage of an eye, gastrointestinal tract, upper and lower respiratory tract. Later, it infects the preauricular, mesenteric and cervical lymph nodes and sometimes the infection also spreads to the visceral organs.
Content: Life Cycle of Adenovirus
- Adenovirus Life Cycle: Stages
- Host cell and Virus Interaction
Adenovirus Life Cycle: Stages
The life cycle of adenovirus includes the following steps:
Adenovirus gets attached to the host cell surface by two-stage interactions, namely:
- Initial interaction
- Secondary interaction
Initial interaction: In this stage, attachment of penton fibre occurs with the host cell receptor. A knob of the fibre protein attaches to the cell receptors of CAR family (Coxsackievirus Adenovirus Receptor). CD46 is the most common receptor, for all the serotypes of adenovirus. The host cell also contains some other receptors like MHC-I, MHC-II molecules and sialic acid residues.
There is a special motif found in the structure of the adenovirus, which refers as “Arginine glycine aspartate motif ”. The configuration of the arginine glycine aspartate motif helps an adenovirus to get internalized into the host cell. Process of internalization is very specific or selective. The αV integrin protein gives a signal for the particular serotype of the virus and results in the induction of actin polymerase to uptake the virus.
The process of internalization of adenovirus by the host cell membrane into the cytoplasm commonly refers to as “Endocytosis”. The binding of Arginine glycine aspartate motif of the penton base with the αV Integrin protein of the host cell results in the endocytosis of the adenovirus. The endocytosis occurs by means of CCPs (Clathrin coated pits) of the host cell membrane. A process of endocytosis also refers to as “Receptor-mediated endocytosis”.
Vesicle Formation: When an adenovirus enters into the host cell, a vesicle forms around it refers to as “Endosome”. And there is a unique feature, where the whole virus gets into the cytoplasm of the host cell rather than the genetic material.
The virion gets released from the endosome as a result of endosome acidification. The acidification of endosome results in a dissociation of the protein particles like fibre and capsid into the cytoplasm. Only the viral DNA moves into the nucleus of the host cell for the process of replication and multiplication.
Replication and Biosynthesis
The viral DNA replicates inside the nucleus. There is a 55KD terminal protein acts like a “Primer”, found attached to the each 5’ end of the viral ds-DNA. This terminal protein initiates the synthesis of viral DNA. In adenovirus, two kinds of replication occur, namely:
- An early phase of DNA replication
- The late phase of DNA replication
The early phase of DNA replication occurs inside the nucleus, which will produce the early genes. The early gene products will undergo transcription to produce early viral mRNA and move it to the cytoplasm of the host cell. A viral mRNA will further undergo translation and will produce the early viral regulatory proteins. Early viral protein brings the S-phase of the host cell.
The late phase of DNA replication occurs inside the nucleus, which will produce the late genes. The late gene products will undergo transcription to produce late viral mRNA in the cytoplasm of a host cell. A viral mRNA will further undergo translation and form the late viral structural proteins.
Bioassembly and Release
After the gene expression of the adenovirus or after the completion of the translation of mRNA, all the virion protein or particles get assembled. The viral DNA is first packaged into the capsid along with penton fibres, refers as the process of “Maturation”. The mature viral progeny finally release out of the host cell either through budding or cell lysis and then infect other cells.
The adenovirus infects the epithelial cells of the respiratory tract, urinary tract, intestinal tract and lining of eyes. When it finds a specific host cell, it starts replicating and undergo multiplication in the epithelial cells of conjunctiva, cornea, pharynx etc.
After infecting the epithelial cells, it can further spread to the regional lymph nodes of the infected person. Usually, an adenovirus infection does not spread beyond the regional lymph nodes but in some cases, can also affect visceral organs.
Host cell and Virus Interaction
The virus progeny release out of the host cell and mainly produce the following types of infection with the host cell:
It also refers as “Lytic infection”. Productive infection can define as the type of infection in which the genome of the virus undergoes complete replication and cause cell death by releasing viral progenies. Symptoms start appearing after a few days of infection.
It can define as the type of infection in which a genome of the virus undergoes incomplete replication. Thus, in abortive infection, a virus is unable to produce viral progenies, but the infection remains persistent to the host cell.
It can define as the type of infection in which the virus particles remain inside the host cells or tissues. In latent infection, the virus particles live in a latent or hidden form, but the symptoms appear when the immunity or resistance of the host cell becomes low.
It is a unique feature of the adenovirus that it shows an oncogenic property. Some serotypes like A and B can transform the host cell into the cancerous cell by integrating its viral DNA.
Some of the adenovirus infections are mild and self-limiting.