Download Are Viruses Alive?

Are Viruses Alive?
Patrick Forterre
Université Paris-Sud (Institut de Génétique et Microbiologie)
Institut Pasteur (Département de Microbiologie)
David
Prangishvili
Spiraviridae
Are Viruses Alive?
Is it an important
issue?
Most virologists assume « implicitely » that viruses are alive
They commonly speak of the « virus life cycle » in their papers
Most biologists don’t care…………..many of them even don’t care
about viruses at all!!
Biologists with philosophic background (and/or interested in
exobiology) usually consider that viruses are not living
(Marc Vanregenmortel, Michel Morange, Purificacion Lopez-Garcia, David
Moreira, Antonio Lazcano, Testart)
Michel Morange
Problems raised by the definition of life,
In « Origins and evolution of life, an Astrobiology perspective », pp3-13
Gargaud, Lopez-Garcia and Martin, eds.
Cambrige University press, 2011
Introduction: « I will show that the recent
suggestion that viruses are alive makes no
sense and obscures discussions about life »
« Examining the case of viruses, the absence of
a definition leaves us defenceless when absurd
statements are made on the living character of
such objects »
«To consider viruses as living creates much
useless confusion »
«viruses remain strict
parasites »
« there is no symmetry
between a virocell and a
ribocell. The first needs the
second: the reverse is not
true »
There is no symmetrie
between carnivors et les
herbivors, The first needs the
second: the reverse is not true
HYPOTHESIS: there is a
psychological aspect in this
debate
We don’t want to be
classified in the same
category than viruses
Ribocentrism
«To consider viruses as living creates much useless
confusion » (Morange)
513 pages
Nothing else on
viruses???
To consider viruses as non
living, but by-products of life led
to ignore them or to
underestimate their role in life
history
My hypothesis: scientists who
consider that viruses are not alive
tend to underestimate (denigrate)
viruses……………and make false
statements
% of genes in gene clusters
of Virus-Plasmid orgin
% of genes in gene clusters
of unknown origin
% other genes
Cortez, Forterre and Gribaldo
Genome Biology, 2009
6%
81%
13%
Ori C
a→c→g→a→t
About 20% of genes in archaeal and bacterial genomes
originated in viruses or plasmids
DePerseval and Heidman, Cytogenet
Genome Res, 2005
viral origin
?
repeated
40%
retrovirusderived
elements)
8%%
retrovirus
2% (exon)
eukaryotic genes
15%
(introns)
Total sequences: 196 kb, 223 genes, 168
different proteins
168 different proteins
103 singletons
PAV1 (18)
TPV1 (24)
pGT5 (3.6)
pRT1 (3.4)
pTN1 (3.3)
pTN2 (13)
pP12-1 (12)
pT26-2 (25)
pAMT11 (20)
pTN3 (18)
PCIR10 (13)
PIRI48 (13)
pEXT9a (10,5)
pIRI33 (11)
pAMT7 (8.5)
36 proteins with homologue(s) in
at least one other plasmid/virus*
(6)
59 with homologues in cellular
genomes*
58 of them being encoded by
genes present in integrated
viruses/plasmids (archaeal
proteins of viral origin)
1 protein of cellular origin
(MCM)
•Mostly in Thermococcales or in Methanococcales or
Thermococcales, one also in Sulfolobus (integrase),
one in an Haloarchaeal plasmid
The gene flux from viruses to cells is a very ancient on-going process : a
lot of cellular proteins should have a viral origin
viruses
cells
Cells are giant pick-pockets
of viral genes
Scientists systematically favour
transfer from cells to viruses in the
interpretation of phylogenetic
analyses.
Implicit (false) assumption: new
genes cannot originated in viral
lineages
RNA polymerase
Ancient cells (fourth domain)
Megavirales
Boyer et al., Plos One, 2011
Williams et al., Plos One, 2011
Modern cells (Eukaryotes)
Ancient Megavirales
Megavirales
Modern cells (Eukaryotes/Archaea)
Many viruses encode DNA replication proteins
that are very divergent from their
cellular homologues
Escherichia coli Topo IV
Bacillus subtilis
Prochlorococcus marinus
Bactéries
Deinococcus radiodurans
Escherichia coli DNA gyrase
Bacteriovirus T4
African Swine Fever (NCLDV)
Chilo iridescent virus (NCLDV)
Virus
Trypanosoma brucei
PBCV-1Chorella virus (NCLDV)
Plasmodium falciparum
Caenorhabditis elegans
Encephalitozoon cuniculi
Saccharomyces cerevisiae
Arabidopsis thaliana
Caenorhabditis elegans
Homo sapiens
Drosophila melanogaster
Eukaryotes
E
Hs
Tb
LEHILLRPDTYIGSVELVTQQMWVYDEDVG-INYREVTFVPGLYKIFDEILVNAADNKQRDP-KMSC-IRVTMIRKQLISIWNN
GKGIP
IEHVLTRPEMYIGSLDTTATPMFIYDEQKGHMVWETVKLNHGLLKIVDEILLNASDNISNRSARMTYIRVTITDTGEITIEND
GAGIP
T4
T4
IEHIKKRSGMYIGSSANETHERFMF----GK--WESVGYVPGLVKLIDEIIDNSVDEGIRTKFKFANK
INVTIKKNNQVTVE
DNGRGIP
Ec
Bs
LDAVRKRPGMYIGDTDDGT---------------------GLHHMVFEVVDNAIDEAL---AGHCKE
IIVTIHADNSVSVQ
DDGRGIP
LEAVRKRPGMYIGSTNSK----------------------GLHHLVWEIVDNSIDEAL---AGYCTD
INIQIEKDNSITVV
DNGRGIP
B
Type IIA DNA
Topoisomerase
s
Topo IB DNA
topoisomerases
Poxviridae
Brochier-Armanet, Gribaldo, Forterre, Biology
Direct, 2008
Bacteria
Eucarya
Archaea
Indiani and O'Donnell Nature Reviews Molecular Cell Biology 7, 751–761 (October 2006) | doi:10.1038/ nrm2022
|
Bacteria
Baculovirus
Archaea/
Eukarya
NCLDV
Herpes
T4
One transfer before LUCA followed by a
non-orthologous replacement in
bacteria
Forterre, P.
Current Opinion in Microbiol. 2002
ancient virosphere
a DNA-LUCA?
BACTERIA
ARCHAEA
EUKARYA
We know that many viruses have « invented » new forms of DNA
C
DNA
HMC
HMC-DNA
To protect their genomes against nucleases encoded by their cellular « hosts
Hypothesis: RNA viruses have invented DNA to protect their genomes.
exactly as some modern viruses have modified their DNA.
ThyA
RNA
U-DNA
RNR
T-DNA
HMC-DNA
ThyA-like
If this is true, viruses have played a major role
in the origin and evolution of modern cells
My hypothesis: scientists who
consider that viruses are not alive
tend to underestimate (denigrate)
viruses……………and make false
statements
The double-jelly-roll fold
The PRD1/Adenovirus lineage
The Hong-Kong fold
The HK97 lineage
Viruses are ancient and co-evolved with their victims, (hosts?)
Prangishvili, Forterre
and Garrett, Nature
Rev Microbiol. 2006
It’s not because scientists who
consider that viruses are not alive
tend to underestimate
them……………that viruses are
alive!!!!
Metagenomic and genomic analyses data have
shown that most genetic information in the
biosphere is probably present in viral genomes and
derived elements (plasmids)
If viruses are not living, this means that most genetic information
on our planet has been created by non living entities!!
Viruses and related elements
(plasmids) are the major source of
variations by manipulating genomes
and creating new functions
Viruses put an enormous
selection pressure. They
control the number and
type of cells in natural
environments……
Viruses are the major
agents of natural selection
Raoult D. and Forterre, P. Nature Rev Microbiol, 2008
Ribosomes Encoding Organisms
Capsid Encoding Organisms
If you get the sequence of a 1 Mb genome from
metagenomic data, this definition allows you to
distinguish between cellular and a viral genomes
Krupovic and Bamford,
J Virol 2010
A virus is defined by its capsid
(the viral self sensu Bamford)
Raoult D. and Forterre, P. Nature Rev Microbiol, 2008
Ribosomes Encoding Organisms
Capsid Encoding Organisms
If you get the sequence of a 1 Mb genome from
metagenomic data, this definition allows you to
distinguish between cellular and a viral genomes
are viruses
organisms?
are viruses alive?
No, if we confuse the virus with the virion
Viruses (virions) are inert until they
encounter cells, they have no
metabolism, they cannot produce
energy
Viruses (virions) can
cristallize (Tobacco mosaic
virus)
Viewed in TV
Chamberlain’s filter
(1884)
VIRUSES and GENES
Jacob and Wollman
Scientific American. 1961 Jun;204:93-107,
A virus may exist in three states:
-the extracellular infectious state
-the vegetative state of autonomous
replication
-the proviral state »
«A virus can be considered a
genetic element enclosed in a
protein coat »
This traditional view of “viruses as virions” has been
criticized by Claudiu Bandea in 1983 and more recently by
Jean-Michel Claverie
The virus should not be confused with the virion
Claudiu Bandea
(Journal of Theoretical Biology,
1983)
Bandea: The living phase of the
virus is the intracellular phase of
its life cycle
Claverie: The virus is the viral
factory
Jean-Michel Claverie
(Genome Biology, 2006)
The viral factory reorganize cell
metabolism, energetic, and all
cell synthetic functions to
produce virions
Mimivirus viral factory
reorganize cell metabolism,
energetic, and all cell synthetic
functions to produce virions
This is not a virus
This are not Humans
This is a virus
These are Humans
Origin of the eucaryotic
nucleus
Takemura, J. Mol. Evol.
2001
Bell, J. Mol. Evol. 2001
Viral factory
the Nucleus of a virocell
nucleus
But…..the concept of viruses as viral factory cannot be
generalized
because viruses infecting archaea and bacteria dont produce
obvious viral factories
The virus transforms
the cell into a viral
factory (Lwoff, 1961)
André Lwoff
The virus transforms the
cell into a virion factory
The organismal form of the
virus is the virion factory
Forterre and Prangishvili,
Research in Microbiology (2009)
Ann N Y Acad Sci. , (2009)
The organismal form of the
virus corresponds to the
infected cell, which has
been transformed into a
new organism = a virocell
The virocell: a cell whose dream is not to
produce two cells but to produce virions
The virion : a vehicle to disseminate viral genes
The virocell : the living form of the virus
Ribosome encoding
organisms (REO)
ribocells
Reproduce by cell division
Capsid encoding organisms (CEO) :
virocells
Reproduce by production of virions
Cells producing virions but that can still
divide are « ribovirocells »
The virocell should not be confused with the virus
The virocell corresponds to one « existential state of the virus »
A virus may exist in three states:
-the extracellular infectious state
-the vegetative state of autonomous
replication
-the proviral state »
Some viruses can infect different hosts, forming different types of virocells
One should not confuse cells and
organisms
Mamavirus
Amoeba
Sputnik
Bacteria
A dynamic RiboVirocell
Forterre: Giant viruses: conflict
in revisiting the virus concept
Intervirology, in press (2010)
A cell can harbor several different living organisms
A living organism is always associated to one
evolutionary lineage with an history that can be
represented by a tree-like structure
Mamavirus
Amoeba
Sputnik
Bacteria
marc van regenmortel
Some viruses that
infect cyanobacteria
and degrade their
chromosomes encode
proteins involved in
photosynthesis to
replace those of the cell
A photosynthetic
virocell
Braggs and
Chisholm, Plos
One, 2008
Virions of
photosynthetic viruses
Genome can be amplified in the virocell from 100 to 1000 times
Mew viral genes (proteins) can originate by: point mutations, duplication,
recombination, slippage, frameshift, overlapping
Viruses are not only vehicules
of cellular genes
New proteins also originated
in viral lineages
Virus-first hypotheses for the origin of life cannot be correct
Viruses cannot have appeared before cells……since they are cells
themselves
But of course viruses might have appeared
before modern cells,
i.e. before LUCA
Schematic history of life
Origin of Life (first « cell »)
First RNA cell
« invention » of the ribosome
First RNA-Protein cell
ORIGIN OF VIRUSES
LUCA
« invention » of DNA
Eukarya
Archaea
Bacteria
A simple hypothesis for the origin of viruses: the ancient escape hypothesis
Different mechanisms triggered the
formation of different types of virions to
disseminate RNA genomes in the late RNA
world (after the invention of proteins).
Some ribocells became ribovirocells
and later on virocells
Forterre and Krupovic,
the origin of virocell,
book chapter, in press
Viruses are evolved by
cells
Moreira and Lopez-Garcia, Nature Rev
microbio (2009)
Viruses evolved within
cells (in the virocell)
Violent reactions to the
virocell concepts
« conceptual trick »
« artifice»
«epistemological cheating»
The remore indeed does
not transform the shark
into a remorashark…!!!!!
The remore stay
outside!!!! Very different
from the virus situation
A more interesting
example: Chlamydiae
The cellular structure of the
Chlamydiae is conserved all
along its life cycle
Unlike viruses, he
Chlamydiae (a ribocell) does
not borrow the cellular
structure of its victim
Viruses have unique life cycle properties that justify the class them in a
categorie different from any other types of cellular parasite (capsid
encoding organisms)
What is life?
It’s not a scientific question
It’s a philosophical question
We need a philosophical framework
My personal philosophical framework
Life is the mode of existence of albuminoïd bodies
Friederich Engels (Dialectics of nature, 1883)
Life is the mode of existence of living organisms
So…what is a living organisms ?
Two approaches:
We decide what is a living organism and
We look if specific biological entities (viruses?) fit with our
definition
We decide which biological entities are living and we
propose a definition based on their properties
2008 :
A collection of integrated organs (molecular machines) producing individuals
evolving through natural selection
2012
A living organism should belong to a evolutionary lineage characterized by a
life cycle with at least one cellular phase
Life
?
?
?
Are plasmids living organisms ?
This is not a bacterial
penis, but a plasmid
made dissemination
system
Plasmids are only made of
nucleic acid. They probably
originated from viruses that lost
their capsid
Bacteria have no sex! It’s a
mode of plasmid dissemination