Viral Life Cycle

Study Notes

The viral life cycle consists of attachment, penetration, uncoating, transcription, translation, genome replication, and assembly and release
Initial infection is followed by an eclipse phase, where all viral particles disappear
Viral genome takes over the host cell's protein-making machinery, directing the production of viral components

The interaction between a virus and its target cell begins with attachment to specific receptors on the cell
Attachment is a critical step in target selection by many viruses
Requires viral attachment protein and cellular receptors

Enveloped viruses:
- Fuse their envelope with the host cell membrane (e.g. Herpesvirus, Paramyxovirus, HIV)
- Taken into the cell via endocytosis
Non-enveloped viruses:
- Penetrate host cells by various mechanisms, including direct penetration and endocytosis

Uncoating of the viral genome leads to the first step of viral replication, i.e., expression of mRNA (transcription)
Translation of mRNA generates "early proteins" which often include synthesis of viral DNA or RNA polymerase and other proteins that play an important role in viral replication
Viral genome replication leads to complementary strand synthesis and additional templates using nucleic acids

One convergent point for all viruses is that they all need to go through mRNA (+ve) strand synthesis to produce proteins
Positive (+ve) nucleic acid (DNA or RNA) is the gene coding strand (or the actual gene sequence)
Negative (-ve) nucleic acid (DNA or RNA) is the complementary strand to the gene coding mRNA (the template strand)

Viral replication is a process of generating new genomes
Special cases require specific viral enzymes:
- RNA-dependent DNA polymerase (reverse transcriptase)
- RNA-dependent RNA polymerase (RNA replicase)

Viral mRNA can be processed with the same range of features that are found on eukaryotic RNA:
- 5'-5' N7-methylguanosine-triphosphate CAP
- Poly A tail (100-200 adenosine residues)
Viruses can either make their own 5' CAP or possess a 3D RNA structure known as internal ribosomal entry site element (IRES)

Different ways of producing viral proteins:
- Transcription of individual mRNA molecules from the genome
- Segmented genome where each molecule gives single mRNA
- Production of a single long polyprotein that is later cleaved into individual functional peptides
- Some viral genomes can be transcribed by "shifting the reading frame" with one or two nucleotides and thus produce different mRNA and proteins

Newly formed virion can be released by different means:
- Budding causes the viral capsid to grab cellular membrane in a form of an envelope which is laced with viral proteins
- Cell lyses caused by lytic viruses

Two possible existing bacteriophages:
- Virulent (lytic) phage kills the host following infection
- Lysogenic (temperate) phage undergoes lysogeny wherein the phage genome becomes a prophage (provirus) either by integration into the host chromosome or exist as an independent entity but replicating with the rate equal to the host genome multiplication

Viral tropism is the ability of a virus to infect a particular cell (cellular tropism), tissue (tissue tropism), or host species (host tropism)
Tropism is defined by few factors:
- Viral glycoproteins (VAP) integrated in the outer coat that target receptors on the surface of the host cells (susceptibility)
- Presence of transcription factors allowing expression of viral genes
- Presence of cell enzyme pathways to produce viral proteins is known as "permissivity"

Enteric viruses: Fecal-oral route (e.g. Enteroviruses, Rotaviruses)
Respiratory viruses: Droplets/aerosol (e.g. Influenza, Rhinoviruses, Measles)
Zoonotic viruses: Vectors (such as arthropods) or animal to human (e.g. Rabies, Influenza A, Flaviviruses)
Sexually transmitted viruses: Sexual contact (e.g. Herpes simplex, HIV, HPV)
Vertically transmitted viruses: Maternal-neonatal transmission (e.g. Rubella, CMV, HIV, HSV)