Enveloped viruses show increased propensity to cross-species transmission and zoonosis

 

Are there fundamental features of a virus that make it more likely to infect multiple hosts, and even make a zoonotic ‘leap’ into humans?

In studies so far, zoonotic risk has been linked to three main factors: viral genetic material (RNA viruses are suggested to be more prone than DNA viruses), site of replication (viruses replicating in the host cytoplasm instead of the nucleus may have an advantage) and genome size (viruses with smaller genomes may be more zoonotic).

However, viruses have another characterising feature. The surface of a virus can be enveloped, i.e. have a membranous coat (which can be destroyed by soap) or they can be enclosed by a fairly rigid protein shell. Curiously, most zoonotic viruses that have impacted human life are enveloped, for example smallpox and monkeypox, coronaviruses, and viruses that cause rabies, measles and flu.

Previous analyses into zoonotic risk were performed on a limited dataset of the mammalian virosphere encompassing only a few hundred viruses and focused on those causing human disease. In this preprint, the authors analyse a large VIRION database comprising 5149 viruses identified through metagenomic studies (i.e. viral genetic material from environmental samples).

 

 

The authors analysed the number of mammalian hosts a virus could infect as function of the following variables: genome size, genome composition (RNA or DNA, single stranded or double stranded, segmented or unsegmented), nuclear or cytosolic location of virus replication, and presence of a viral envelope.

They first looked at the probability of a virus infecting multiple non-human mammalian hosts. They found that this cross-species transmissibility was significantly linked with the presence of a viral envelope, while the other factors had little impact (Figure, top panel).

When the specific scenario of zoonosis was analysed, that is by focusing on human host infection in the analyses, it also strikingly showed a strong impact of the viral envelope (Figure, bottom panel). They find a 2.5-fold increase in likelihood of zoonosis in enveloped viruses compared to non-enveloped ones, which constitutes a novel finding.

Interestingly, the analyses of zoonotic probability also brought out other factors that have been previously reported and may play a role in successful human infection. Viruses that undergo cytoplasmic replication were found to be 1.9 times more likely to be zoonotic, and viruses with smaller genomes and segmented genomes may also have a slight advantage.

What I like about this preprint:

The message of this preprint is clear and simple, and the finding is likely very important. What a virus can do is typically ascribed to its genome or its proteins, particularly those on the surface. The supposedly delicate membrane enveloping the virus may have not received its due attention. It will be exciting to see what the mechanistic basis of this analysis turns out to be.

Questions for the authors:

Some clarifications on the analysis:

1. In Figure 2a: are all these viruses non-zoonotic or were the human hosts simply not counted in the number of hosts infected?
2. How do you separate a mixed effect of variables? For example, have you compared a subset of enveloped vs non-enveloped viruses while keeping other variables the same?
3. Figure 2a shows a trend opposite to what is stated in the text – ds genomes have a marginally higher probability for multi-host infection?

Some questions about the dataset:

4. How much structural information is available on the viruses in the VIRION dataset? Would it be possible that some of the viruses in the non-enveloped category do have membranes in their outer surface?
5. Would it be possible to test for other features of a virus life cycle and their­­ correlation to zoonosis, for example the length of viral replication cycles and whether they have lytic or non-lytic modes of spread?

 

Posted on: 29 August 2022 , updated on: 30 August 2022

doi: https://doi.org/10.1242/prelights.32604

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