The Mechanisms of Virus-Host-Interaction during Infections
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| License | CC Attribution 3.0 Unported: You are free to use, adapt and copy, distribute and transmit the work or content in adapted or unchanged form for any legal purpose as long as the work is attributed to the author in the manner specified by the author or licensor. | |
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Transcript: English(auto-generated)
00:07
I study viruses. There is hardly any person in this world whose life hasn't been affected by viruses in the past year. This pandemic has been a very cruel reminder of how important it is to understand how are the mechanisms underlying the interaction
00:23
between a virus and its host during an infection. But viruses do not only infect humans and animals, they also infect all organisms across the three domains of life, which means that they infect eukaryotic cells, but they also infect archaea and bacteria. Traditionally, viruses have always been seen as a killing machine,
00:43
which infect the host, reproduce itself, and then lies the host in the process, which is known as a lytic cycle. However, in recent years, there's been a change in the paradigm because viruses can also have different life cycles and they can also possibly have positive effects
01:00
on host evolutionary trajectory. So for example, viruses can produce lysogenic life cycles where they inject their genome and it's integrated into the host chromosome and viruses reproduce along with the cells until there is some environmental trigger that produces that the virus goes from this lysogenic into the lytic cycle.
01:20
Alternatively, the host can find a way to remove the infectivity modules out of the viral genome and the genetic information of the virus remains integrated into the host chromosome as an inactive pro-virus. Also, viruses can produce chronic life cycles and this means that a virus infects a cell and constantly produces progeny,
01:41
but without lies of the host. And this is a particularly interesting life cycle because it shows us that viruses and hosts have found a way to coexist where both can be successfully reproducing themselves and coexist in time. Particularly, a research focus in archaea viruses
02:01
which is one of the most diverse group and yet least studied. And it's a group where these chronic life cycles seems to be rather the norm than the exception. Our research aims to understand how this chronic infection occurs and how the virus and the host interact during the infection. And also, we aim to understand
02:21
how this long-term relationship of virus and host impacts the coevolution of these two partners. To answer our research question, first, we need to establish a very stable system of virus and host that we can reproduce and manipulate in the laboratory.
02:40
Second, we need to characterize this chronic infection and assess what is the outcome of it for the host and the virus. And third, we need to identify the specific genes and what are the mechanisms underlying this chronic infection and that allows this coexistence in time between the host and the virus.
03:01
For this, first, we have to go to the field and take environmental samples to try to enrich archaea viruses out of it. Because chronic infections are rather rare and very complicated to detect, we have to develop specific methods to detect them in these samples. To do this, first, we went to the field
03:21
and took environmental samples to generate enrichments of these viruses that infect these archaea and produce chronic infection. Then we have to develop a method to actually be able to detect these chronic infections into the samples because all of the traditional culturing methods are designed to detect only lytic infections,
03:41
which means that the host is being killed. Secondly, we combine classic molecular techniques such as quantitative PCR, which allows us to assess how much is the viral protein that's being produced and what is the outcome for the host and the virus in this chronic infection, and combine it with next-generation sequencing techniques
04:02
such as RNA sequencing, which allows us to identify specific genes in the host genome that are being up or down-regulated by the viral infection. Then we also combine this with proteomics, which allows us to identify specific structural proteins of the virus that are important and extremely relevant
04:22
for virus and host interaction. Altogether, this culturing molecular and next-generation sequencing techniques allows us to assess specifically what is the outcome of the viral infection for the virus and for the host and what are the specific mechanisms underlying this interaction.
04:43
So what we found is that this viral infection that we were characterizing was nothing like any other chronic infection reported to date. First, the virus produced an incredibly high amount of viral particles. This means that the virus is producing a progeny
05:00
which is comparable to a lytic infection but without actually killing the host. Then, when we look at the metabolism of the cell, we discover that the viral infection completely reprograms the transcriptional program of the cell. This means that more than one-third of the genome of the host is actually being differentially expressed
05:22
under viral infection. But this is not a random process. We discover that specifically viral-like sequences already present in the genome of the host are being targeted by this downregulation of the virus. These viral-like sequences are thought to be remnants of old infections
05:41
that actually the host has been able to overcome and they integrate these genes into its own genome in order to provide some unknown selective advantage. What we did then was to generate mutant strains for these viral-like regions in the host chromosome. And what we observed when we infected with our virus
06:01
was that there was a much more acute symptoms of this viral infection which translate into a very strong growth retardation. Altogether, this means that this viral-like region already present in the host chromosome encodes for a new and unknown defense mechanisms that not only provides defense for the host
06:21
but also allows the development of this coexistence between the virus and the host. Up to date, chronic infections have been thought to be something rare in nature and that they have little effect in the host and they have low outcomes in terms of viral progeny.
06:40
However, what we discover is that our virus can completely reshape the host metabolism and they can produce incredibly high amounts of viral particles. Even more interestingly, we discovered that the outcome of the infection heavily depends on virus-virus interaction between the infecting virus and the viral-like sequences already present in the host.
07:01
This opens a whole new dimension that needs to be studied in order to understand virus-host interaction because these viral-like sequences represent a positive trait for the host which allows them to actually establish this coexistence where both virus and host can reproduce and profit.
07:23
So far, we have characterized that these viral-like sequences mediate virus-host interaction. However, we are yet to identify the specific genes and the underlying metabolic and molecular mechanism behind this defense system. Finding out these specific genes
07:40
and understanding the virus-virus interaction could provide a very useful tool because we could, for example, regulate the outcome of a viral infection. But not only that, this also opens the door to look for new solutions for viral diseases through viral-viral interaction-based therapies.