The Science News on Monday

Today in "News on Monday" : 

Please tell us what is the difference between an 
invertebrate cell & a vertebrate cell !   

Published: 2011, PlosPathogens                       

Virus: Nidovirus, Coronavirus, Nam Dinh virus (NDiV), Vietnam

Host species: Insects, mosquito

Aim of the study: 

To compare the genome organization and main enzymatic activities of the first insect-born nidovirus with known representatives of the Nidovirales

Gen /protein of interest: 

nsp14 Exonuclease (ExoN) , nsp15 Endoribonuclease (EndoU)

Main discovery in 2 sentences: 

1) The acquisition of an ExoN is a prerequisite for the evolution of large RNA-genomes

2) The EndoU is not a nidovirus-specific marker, as it is not present in insect-born nidoviruses

Implications for the field: 

1) Studies on CoV-MHV and SARS with defective ExoN demonstrated that while replication kinetics and viability of the mutants were only mildly affected, the mutation rate and frequency was significantly elevated throughout the genome. Furthermore, in vitro studies revealed that the 3'-to-5' ExoN is able to excise single nucleotide at the 3' end of RNAs, thus implicating a role as a proofreading enzyme, which was until then only know for the DNA-world. The discovery of the insect-nidovirus with a intermediate genome size of 20.2 kb and its possession of an ExoN is a major step in CoV-research, as it marks the bottom line of a "large-Nidovirus" possessing an ExoN. With its discovery, the gap to the next known RNA-virus lacking an Exon could be reduced to only 0.8 kb. To conclude, ExoN confers very high replication fidelity which is needed for the maintenance of a very large and complex genome size. 

                       

Secondly, it was believed that the endoribonuclease (a nuclease that cleaves cellular or viral RNA) was unique to Nidoviruses and was thus proposed to be a nidovirus-wide marker. However, the discovery that the newly identified insect-virus NDiV and also Roniviruses (invertebrate-virus, replicates in crustaceans) dont possess an EndoU-activity contradicts this hypothesis. As Roniviruses belong to the large nidoviruses, it can be considered unlikely that the EndoU is involved in RNA-proofreading and replication. 

The biochemical characteristics of the EndoU-activity of Coronaviruses or arteriviruses are very well discribed, however its function  during virus-replication and its involvement in innate immune evasions is unknown.

Remaining questions:

1) Is it possible to further reduce the gap between RNA-viruses with and without ExoN-activity?

2) Is the ExoN involved in innate immune evasion?

3) why do invertebrate-Nidoviruses (irrespectively of their genome-size) not encode an EndoU?

4) what is the difference during virus replication in a vertebrate and in a vertebrate cell?

Plus factor of the paper: 

The discovery of a first insect-born Nidovirus is a very important step in this field, as it opens the possibility to compare viruses from the same order that have a different host range. Furthermore, the genome-wide comparison between known vertebrate nidoviruses and NDiV was executed in very detail, as all important enzymes were discussed separately. The discovery of Nidoviruses without an EndoU is very crucial for further work on EndoU activity and this will surely give very interesting insights into the replication of viruses with different host range.

Drawback of the paper:

Generally, the paper is well written, but quite long and especially the discussion is very extensive and could have been reduced without any loss of content. Furthermore, more in depth implications of the present work were missing.