Virus‐derived small RNAs: molecular footprints of host–pathogen interactions

Abstract

Viruses are obligatory intracellular parasites that require the host machinery to replicate. During their replication cycle, viral RNA intermediates can be recognized and degraded by different antiviral mechanisms that include RNA decay, RNA interference, and RNase L pathways. As a consequence of viral RNA degradation, infected cells can accumulate virus-derived small RNAs at high levels compared to cellular molecules. These small RNAs are imprinted with molecular characteristics that reflect their origin. First, small RNAs can be used to reconstruct viral sequences and identify the virus from which they originated. Second, other molecular features of small RNAs such as size, polarity, and base preferences depend on the type of viral substrate and host mechanism of degradation. Thus, the pattern of small RNAs generated in infected cells can be used as a molecular footprint to identify and characterize viruses independent on sequence homology searches against known references. Hence, sequencing of small RNAs obtained from infected cells enables virus discovery and characterization using both sequence-dependent strategies and novel pattern-based approaches. Recent studies are helping unlock the full application of small RNA sequencing for virus discovery and characterization. WIREs RNA 2016, 7:824-837. doi: 10.1002/wrna.1361 For further resources related to this article, please visit the WIREs website.

The small non-coding RNA response to virus infection in the Leishmania vector Lutzomyia longipalpis

“…The broad size profile of small RNAs derived from the viruses we described before suggest that they had the ability to inhibit the siRNA pathway in L . longipalpis rather than the absence of such response [ 55 ]. We note that most studies on the natural antiviral role of RNAi in vector insects have focused on arboviruses that have positive-stranded RNA genomes [ 22 , 34 , 35 , 56 , 57 ].…”

The insect reservoir of biodiversity for viruses and for antiviral mechanisms

“…The major antiviral RNAi pathway is the small interfering (si) RNA pathway. It involves the RNaseIII enzyme Dicer-2, which senses replicating viral RNAs and processes them into 21 nucleotide (nt)-long siRNAs (reviewed in Paro et al 2015, Aguiar et al 2016). These siRNAs originate from both the genome and the antigenome of the virus, as observed during infection by the rhabdovirus Vesicular Stomatitis virus (VSV) in the model organism Drosophila melanogaster and the sandfly Lutzomyia longipalpis, which is one natural vector for this arthropod-borne virus ( Figure 2) (Mueller et al 2010, Marques et al 2013, Ferreira et al 2018.…”

Occurrence of Small Homologous and Complementary Fragments in Human Virus Genomes and Their Possible Role

“…Выбор длины фрагментов в 21 нуклеотид был мотивирован с распространенностью ее у мвРНК [4], длиною малых интерферирую-щих РНК эукариот [12] и последовательностей в tracrRNA (адаптивная система CRISPR/Cas бактерий и архей), которые осуществляют ком-плементарное связывание с геномом фагов [5], и внРНК вируса гриппа А [13,14,20].…”

“…Хотя длина, полярность и нуклеотидный состав мвРНК ва-рьировали в зависимости от вирусного субстра-та и механизма деградации их хозяином, среди них четко выступало преобладание мвРНК раз-мером в 20-23 нуклеотидов. Характерно, что появление мвРНК у разных животных часто обнаруживает профиль, соответствующий ак-тивации образования малых интерферирующих РНК [4]. В этой связи возник вопрос, не могут ли содержатся у вирусов среди их мвРНК такие, которые гомологичны или комплементарны по-следовательностям генома другого вируса или аутокомплементарны.…”