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Saturday, July 11, 2020

The coronavirus life cycle

The coronavirus life cycle is depicted in a figure from Fung and Liu (2019). See below for a brief description.
The virus particle attaches to receptors on the cell surface (mostly ACE2 in the case of SARS-CoV-2). It is taken into the cell by endocytosis and then the viral membrane fuses with the host membrane releasing the viral RNA. The viral RNA is translated to produce the 1a and 1ab polyproteins, which are cleaved to produce 16 nonstructural proteins (nsps). Most of the nsps assemble to from the replication-transcription complex (RTC). [see Structure and expression of the SARS-CoV-2 (coronavirus) genome]

RTC transcribes the original (+) strand creating (-) strands that are subsequently copied to make more viral (+) strands. RTC also produces a cluster of nine (-) strand subgenomic RNAs (sgRNAs) that are transcribed to make (+) sgRNAs that serve as mRNAs for the production of the structural proteins. N protein (nucleocapsid) binds to the viral (+) strand RNAs to help form new viral particles. The other structural proteins are synthesized in the endoplasmic reticulum (ER) where they assemble to form the protein-membrane virus particle that engulfs the viral RNA.

New virus particles are released when the vesicles fuse with the plasma membrane.

The entire life cycle takes about 10-16 hours and about 100 new virus particles are released before the cell commits suicide by apoptosis.

Fung, T.S. and Liu, D.X. (2019) Human coronavirus: host-pathogen interaction. Annual review of microbiology 73:529-557. [doi: 10.1146/annurev-micro-020518-115759]


Woody Benson said...

Thanks for the explication and pdf-source. You have corrected a number of misconceptions I have had about Covid-19.
Perhaps you could answer a question for me. I have been impressed by the high positive rates in some Covid-19 antibody studies. In particular, Brazilian workers have reported between 15%-25% positives for population samples along the Amazon River: Sampling in Belem, Manaus, and towns on the upper Rio Negro, unexpectedly (in my judgement) with the highest values at the most isolated site. People in these forest towns and villages are especially liable (in my experience) to come down with unspecified fevers, seemingly transmitted by mosquitos and other biting bugs, that in a few days go away. My question is whether some of the antibodies induced by a "shotgun" of virus types circulating in tropical forests could be detected by Covid-19 tests and result in an excess of false positives in these places?

Larry Moran said...

I don't know.

Joe Felsenstein said...

You gave a mutation rate of 1 in 10^6 per replication. There are 30,000 bases in the genome. So that should be 0.03 per genome per virus replication. People around here who study Covid-19 give one mutation per 2 persons in a chain of infection as the rate of change. Are these figures consistent with each other? I suppose it depends on how many replications of the virus there are in a chain of infection from one person to another. If it were about 15 these numbers might be consistent.

Larry Moran said...

Most of the genome codes for the various proteins so I imagine that many mutations are detrimental and won't be picked up in transmissions. I think the best estimates are that roughly 40% of mutations in coding regions are detrimental.

This means that the measured rate of change will be about half of the predicted value from the mutation rate, right?

Each cell releases about 100 virus particles so that's an average pf 50 replications. I imagine that there have to be about 10 cycles before one of the virus particles infects someone else. This would take about 50-60 hours.

That's 500 replications so it looks like you are right - the numbers don't seem consistent.

Joe Felsenstein said...

Each cell releases about 100 virus particles so that's an average pf 50 replications.

I wouldn't calculate it that way. We want to consider a lineage. If I get infected from you, the number of all replications in you is not relevant -- only the ones in the lineage from the virus particle that infected you to the one that infected me. In a single cell bursting and releasing 100 virus particles, each one has undergone maybe 7 replications since the particle that infected that cell. The other replications are not to be counted. Then there is the issue of how many cell bursts are on the lineage from your infection to mine. Again, most of the ones in you are irrelevant to that as they are not in that lineage.

Joe Felsenstein said...

The first line of the previous comment is a quote from Larry.

mobathome said...

I have heard of junk DNA/RNA in mammals. Do we know whether there is junk DNA/RNA in the payload of viruses? A quick search did not help me answer that question. I did learn that "[m]any DNA and RNA viruses synthesize their own ncRNAs," but not much else.

Barbara said...

Possibly relevant: Small towns in eastern Oregon had low rates of COVID-19 for a long time, but then the rates in some town rose dramatically. Why? Apparently because in small towns, nearly everyone visits the same grocery store, the same feed store, the same cafe regularly. So once one carrier gets to town, the virus may get to most people fairly quickly.

Plus, of course, issues of not wearing masks, of continuing to meet in church without masks, etc.

Nick Alcock said...

Oh wow in hindsight this comment is disturbing :( with the benefit of hindsight, we can say *definitely not*. This was early signs of what is now known as the immune-escaping Brazilian variant on the march.