Question

How does each of the following viruses deal with issues and problems related to translation initiation, expression of downstream cistrons and fine-tuning of gene expression?

Influenza A virus

Rhabdovirus eg VSV

Answer 1

Influenza A Virus

Translational initiation: generally, virus do not contain components to initiate translation and have to be dependent on the host machinery. In case of Influenza virus, it performs a “cap-snatching” event at the 5’ end of its own mRNA, which is capping its 5’ end derived from host cell pre-mRNA. The cap is followed by a common viral sequence and ends at 3’ with polyA tail. A viral polymerase selectively binds to the viral mRNA. Once recognition of the polymerase is complete, translation is initiated without the need for initiation factor eIF4e. Thus, Influenza A virus brings about its own translation without the need for host mRNA or initiation factor.

Fine-tuning of gene expression: Viral RNA transcription, replication and genome packaging is controlled by segment specific non-coding regions (NCR) in the genome of Influenza A virus. There are eight such segments in total that regulate viral synthesis and protein expression at levels of transcription and translation. The presence of Kozak sequence at -3 position in a NCR PB1 caused multiple- cycle replication reduction and proved its role in fine tuning replication as well as host recognition in Influenza virus.

Rhabdovirus

Translation initiation: Initiation is brought about by transcript-specific translation mechanism, that is facilitated by ribosomes. Cap-dependent translation in vesicular stomatitis virus (VSV) requires large ribosomal subunit protein rpL40, which forms 80S on the mRNA of VSV through cis-regulatory element. The function of ribosome as a translational regulator has been explored by the virus belonging to Mononegavirales, apart from its otherwise catalytic role in protein synthesis.

Expression of downstream cistron: Addition of extra 1 or 2 cistrons at downstream position at G genes in Rhabdovirus does not affect virus propogation. Reverse genetics can be employed for understanding of the attenuation process, that is if at all involved in the attenuation process by cistron synthesis and addition.

Fine tuning of gene expression: Transcription attenuation phenomenon occurs in Rhabdovirus, which is a pause that happens due to unadenylated leader RNA and further RNAs being polyadenylated. While the exact mechanism is still unclear, it is believed that attenuation governs transcription and protein expression in the replicative cycle of a Rhabdovirus. Non-segmented negative-sense RNA viruses express genes by sequential synthesis of monocistronic m RNAs and involves formation of a transcription gradient due to gene border attenuation.