Virus Inheritance and Mutation

Viral Replication

The viral infection process approximately consists of five stages in the host cells: attachment, penetration, replication, release. In the stage of replication. Viruses according to the Baltimore classification (BC) employ different replication strategies respectively.

• DNA viral replication.

Most DNA viruses replicate inside the host cell nucleus and utilize host cellular machinery for their reproduction. Upon entry into the cell, the double-strand DNA (dsDNA) is transported to the nucleus and utilizes host cell polymerase for their replication. The dsDNA can replicate to produce viral dsDNA or serve for mRNA transcription to produce more polyprotein. In the case of single-strand DNA (ssDNA) viruses, the mechanism is the same as dsDNA except for the process in which ssDNA is transcribed to dsDNA and then replicated to produce viral mRNA inside the nucleus.

• RNA viral replication.

In RNA viruses, the process is more complex. The type of RNA they possess (dsRNA,+ssRNA, or -ssRNA) determines whether they are transcribed, translated, or replicated upon viral entry into the host. In the case of dsRNA and -ssRNA they have to synthesize the viral +ssRNA and mRNAs to be recognized by host cell machinery. For this purpose, they encode their own RNA-dependent RNA-polymerases (RDRP).

• dsRNA. The genome is transcribed by virion packaged polymerase. mRNA is translated to viral proteins or transcribed to complementary strands to yield double-stranded RNA genomes for new virion formation.
• +ssRNA. Genomic RNA serves as templates for the synthesis of complementary full-length (-) strand RNA by a viral polymerase. (-) strand RNA serves as a template for (+) strand RNA. These (+) strands can then serve to produce more polyprotein or as the genome of new virions which are forming.
• -ssRNA. Transcription of (-) strand occurs after entry and is mediated by virion packaged transcriptase. (+) strand RNA is produced and proteins are synthesized. Full-length (-) strand RNA are produced and packaged into newly forming virions.
• Retro-viral replication

ssRNA and dsDNA retroviruses which replicate via DNA/RNA intermediates use a different mechanism for replication. dsDNA viruses upon entry into the host are transported into the nucleus and utilize host cell machinery for translation. Upon assembly of virus particles into virions, the reverse transcription occurs which converts RNA to RNA/DNA complex which is then reverse transcribed to circular dsDNA by viral RNA dependent DNA polymerase (reverse transcriptase). In the case of ssRNA retrovirus, ssRNA is reversely transcribed to dsDNA inside the virion upon cell entry which is then transported to the host nucleus for integration and transcription.

Virus Variations

Viruses have three main mechanisms of variation. Any of the three mechanisms may result in viruses that have new biological properties, such as a new host range and pathogenic potential.

• Mutation: The virus mutation includes point mutation, insertion or deletion of nucleotides, and recombinant. During replication, point mutations are incorporated into one or more genomic positions as a result of a lack of proof-reading activity of the viral polymerase. Viral mutation rates are not merely caused by polymerase errors, but also by host enzymes, spontaneous nucleic acid damage, and even special genetic elements located within some viral genomes whose specific function is to produce new mutations. RNA viruses were shown to evolve faster than DNA viruses since they lack the proof-reading mechanism of viral RNA-dependent RNA polymerase.
• Recombination: foreign genetic material is incorporated into the viral genome through mechanisms such as template switching during replication.
• Reassortment: occurs on dual infection of a cell with segmented genome viruses, whole gene segments can be swapped.

Fig.1 Molecular mechanisms for generating viral diversity. (Arellano-Galindo, 2012)

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Reference

1. Arellano-Galindo, J.; et al. Point mutations and antiviral drug resistance. InTech. 2012.