Megavirus
Encyclopedia
Megavirus is a viral
genus containing a single identified species named Megavirus chilensis (MGVC), phylogenetically related to Acanthamoeba polyphaga Mimivirus
(APMV). In colloquial speech, MGVC is more commonly referred to as just “Megavirus”. It has the largest capsid
diameter of all known viruses, as well as the largest and most complex genome
among all known viruses.
, near the marine station in Las Cruces, by Prof. Jean-Michel Claverie and Dr. Chantal Abergel from the Structural & Genomic Information laboratory (IGS, CNRS and Aix-Marseille University). Researchers from this laboratory were already involved in the characterization of Mimivirus, the first described giant virus 2. Megavirus was isolated by co-cultivation with a variety of Acanthamoeba
laboratory strains (A. polyphaga, A. castellanii, A. griffini) following a protocol pioneered by Dr. Timothy Rowbotham for isolating intracellular parasitic bacteria. Megavirus’ natural host, likely a marine or brackish water phagocytic protozoan, is not known.
, but will be proposed as a member of the Megaviridae, a new family constituted of the large DNA viruses the genome of which is around a million base pairs in length. Members of this new family defined by a number of common specific features (Table 1 and 2) will include various viruses likely to share a common ancestor with Mimivirus and Megavirus, although their present genome size was reduced below 1 Mb. Megavirus also joins a group of large viruses known as nucleocytoplasmic large DNA viruses
(NCLDV), although this term appears increasingly inappropriate to designate viruses replicating entirely within the cytoplasm of their hosts through the de novo synthesis of large virion factories. Megavirus and Mimivirus share 594 orthologous genes, mostly located within the center segment of their genomes. At the amino-acid sequence level, the corresponding proteins share an average of 50% identical residues.
diameter of 440 nanometre
s (as seen by electron microscopy on thin sections of epoxy resin inclusions), enclosed into a solid mesh of bacterial-like capsular material 75 nm to 100 nm thick. The capsid appears hexagonal, but its icosahedral symmetry is imperfect, due to the presence of the “stargate”, at a single specific vertex of the icosahedron. The stargate is a five-pronged star structure forming the portal through which the internal core of the particle is delivered to the host's cytoplasm. This core is enclosed within two lipid membranes in the particle, also containing a large and diverse complement of viral proteins (e.g. the all transcriptional complex).
with 1,259,197 base pairs in length. This makes it the largest viral genome deciphered so far, outstripping the next-largest virus genome of Mamavirus by 67.5 kb. Prior validation of its transcriptome, it is predicted to encode 1,120 protein-coding genes, a number largely above the one exhibited by many bacteria.
However, beyond an incremental change in size, the Megavirus genome exhibits 7 aminoacyl tRNA synthetases (Table 2), the archetypes of enzymes previously thought only to be encoded by cellular organisms. While 4 of these enzymes were already present in Mimivirus and Mamavirus (for tyrosine, arginine, cysteine, and methionine), Megavirus is exhibiting three more 3 (for tryptophane, asparagine, and isoleucine). Interestingly, the unique aminoacyltRNA synthetase encoded by Cafeteria roenbergensis virus
corresponds to the one for isoleucine. Megavirus also encodes a fused version of the mismatch DNA repair enzyme MutS, uniquely similar to the one found in the mitochondrion of octocorals. This puzzling MutS version appears to be a trademark of the Megaviridae family. Like Mimivirus and CroV, Megavirus contains many genes for sugar, lipid and amino acid processing, as well as some metabolic genes not found in any other virus.
As expected from a virus encoding its own complete DNA replication, repair, and transcription machinery, the host nucleus does not appear to be involved in any of Megavirus replication stages, as already seen for Mimivirus.
Second, the presence of three additional aminoacyltRNA synthetases in the Megavirus genome, with a total of seven, definitely rules out their independent acquisition by lateral transfer from a host. In addition, the phylogenic analysis of their amino acid sequences does not cluster them with any known protozoan clade, but rather connect them deeply to eukaryotic domain.
The conclusion then becomes inescapable that the genome of these giant viruses originated from an ancestral cellular genome (thus endowed of a translation apparatus, with all 20 aminoacyl tRNA synthetases) from which today’s Megaviridae derived by a number of lineage specific genome reduction events, a scenario akin to the one followed by all parasitic organisms. As indicated by the deep rooting of their phylogeny, the Megaviridae lineage might be very old, eventually predating the emergence of modern eukaryotes, or be contemporary and/or linked to the emergence of the nucleus. 5 Alternatively, it could be derived from an extinct cellular domain (the controversial 4th domain of the Tree of Life), many genes of which would have managed to persist in today’s giant viral genomes.
Viral
The adjective or adverb viral and the noun virality may refer to any viral phenomenon, that is, an object or pattern that is able to induce some agents to replicate it, resulting in many copies being produced and spread around....
genus containing a single identified species named Megavirus chilensis (MGVC), phylogenetically related to Acanthamoeba polyphaga Mimivirus
Mimivirus
Mimivirus is a viral genus containing a single identified species named Acanthamoeba polyphaga mimivirus , or is a group of phylogenetically related large viruses . In colloquial speech, APMV is more commonly referred to as just “mimivirus”...
(APMV). In colloquial speech, MGVC is more commonly referred to as just “Megavirus”. It has the largest capsid
Capsid
A capsid is the protein shell of a virus. It consists of several oligomeric structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may not correspond to individual proteins, are called capsomeres. The capsid encloses the genetic...
diameter of all known viruses, as well as the largest and most complex genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
among all known viruses.
Discovery
Megavirus was isolated from a water sample collected in April 2010 off the coast of ChileChile
Chile ,officially the Republic of Chile , is a country in South America occupying a long, narrow coastal strip between the Andes mountains to the east and the Pacific Ocean to the west. It borders Peru to the north, Bolivia to the northeast, Argentina to the east, and the Drake Passage in the far...
, near the marine station in Las Cruces, by Prof. Jean-Michel Claverie and Dr. Chantal Abergel from the Structural & Genomic Information laboratory (IGS, CNRS and Aix-Marseille University). Researchers from this laboratory were already involved in the characterization of Mimivirus, the first described giant virus 2. Megavirus was isolated by co-cultivation with a variety of Acanthamoeba
Acanthamoeba
Acanthamoeba is a genus of amoebae, one of the most common protozoa in soil, and also frequently found in fresh water and other habitats. The cells are small, usually 15 to 35 μm in length and oval to triangular in shape when moving. The pseudopods form a clear hemispherical lobe at the anterior,...
laboratory strains (A. polyphaga, A. castellanii, A. griffini) following a protocol pioneered by Dr. Timothy Rowbotham for isolating intracellular parasitic bacteria. Megavirus’ natural host, likely a marine or brackish water phagocytic protozoan, is not known.
Classification
Megavirus is not yet classified by the International Committee on Taxonomy of VirusesInternational Committee on Taxonomy of Viruses
The International Committee on Taxonomy of Viruses is a committee which authorizes and organizes the taxonomic classification of viruses. They have developed a universal taxonomic scheme for viruses and aim to describe all the viruses of living organisms. Members of the committee are considered to...
, but will be proposed as a member of the Megaviridae, a new family constituted of the large DNA viruses the genome of which is around a million base pairs in length. Members of this new family defined by a number of common specific features (Table 1 and 2) will include various viruses likely to share a common ancestor with Mimivirus and Megavirus, although their present genome size was reduced below 1 Mb. Megavirus also joins a group of large viruses known as nucleocytoplasmic large DNA viruses
Nucleocytoplasmic large DNA viruses
The nucleocytoplasmic large DNA viruses or NCLDV refers to a number of families of large eukaryotic DNA viruses:# Asfarviridae# Iridoviridae# Marseilleviridae# Megaviridae# Mimiviridae# Phycodnaviridae# Poxviridae...
(NCLDV), although this term appears increasingly inappropriate to designate viruses replicating entirely within the cytoplasm of their hosts through the de novo synthesis of large virion factories. Megavirus and Mimivirus share 594 orthologous genes, mostly located within the center segment of their genomes. At the amino-acid sequence level, the corresponding proteins share an average of 50% identical residues.
Structure
The Megavirus particle exhibits a protein capsidCapsid
A capsid is the protein shell of a virus. It consists of several oligomeric structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may not correspond to individual proteins, are called capsomeres. The capsid encloses the genetic...
diameter of 440 nanometre
Nanometre
A nanometre is a unit of length in the metric system, equal to one billionth of a metre. The name combines the SI prefix nano- with the parent unit name metre .The nanometre is often used to express dimensions on the atomic scale: the diameter...
s (as seen by electron microscopy on thin sections of epoxy resin inclusions), enclosed into a solid mesh of bacterial-like capsular material 75 nm to 100 nm thick. The capsid appears hexagonal, but its icosahedral symmetry is imperfect, due to the presence of the “stargate”, at a single specific vertex of the icosahedron. The stargate is a five-pronged star structure forming the portal through which the internal core of the particle is delivered to the host's cytoplasm. This core is enclosed within two lipid membranes in the particle, also containing a large and diverse complement of viral proteins (e.g. the all transcriptional complex).
Genome
The Megavirus chilensis genome is a linear, double-stranded molecule of DNADNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
with 1,259,197 base pairs in length. This makes it the largest viral genome deciphered so far, outstripping the next-largest virus genome of Mamavirus by 67.5 kb. Prior validation of its transcriptome, it is predicted to encode 1,120 protein-coding genes, a number largely above the one exhibited by many bacteria.
However, beyond an incremental change in size, the Megavirus genome exhibits 7 aminoacyl tRNA synthetases (Table 2), the archetypes of enzymes previously thought only to be encoded by cellular organisms. While 4 of these enzymes were already present in Mimivirus and Mamavirus (for tyrosine, arginine, cysteine, and methionine), Megavirus is exhibiting three more 3 (for tryptophane, asparagine, and isoleucine). Interestingly, the unique aminoacyltRNA synthetase encoded by Cafeteria roenbergensis virus
Cafeteria roenbergensis virus
Cafeteria roenbergensis virus is a giant virus that infects the marine zooplankton Cafeteria roenbergensis . CroV has the largest genome of any known marine virus, consisting of ~730,000 base pairs of double-stranded DNA...
corresponds to the one for isoleucine. Megavirus also encodes a fused version of the mismatch DNA repair enzyme MutS, uniquely similar to the one found in the mitochondrion of octocorals. This puzzling MutS version appears to be a trademark of the Megaviridae family. Like Mimivirus and CroV, Megavirus contains many genes for sugar, lipid and amino acid processing, as well as some metabolic genes not found in any other virus.
Replication
Megavirus replication stages closely follows the one already described for Mimivirus. Following rapid engulfing by phagocytosis, and the delivery of the particle core to the cytoplasm, begins the eclipse phase. A closer examination indicates the presence of cytoplasmic “seeds”, of sizes comparable to the most internal membrane-enclosed core of the Megavirus particle. These seeds then develop in full bloomed virion factory over the following 14 hours. The full course of infection (until the complete lysis of the amoebal cells) takes 17h in average, compared to 12 h for Mimivirus. The average number of released Megavirus particles (i.e. the “burst size”) is about half the thousand produced by Mimivirus.As expected from a virus encoding its own complete DNA replication, repair, and transcription machinery, the host nucleus does not appear to be involved in any of Megavirus replication stages, as already seen for Mimivirus.
Implications of discovery
Two Megavirus specific features are of fundamental importance. First, even if its new record-sized genome only represent a small 6% increment compared to the second largest Mamavirus genome, it indicates that we have not yet reached the limit of viral genome sizes, and that even more complex viruses may remain to be discovered, most likely in aquatic environments, the viral diversity of which has been barely scratched by recent metagenomic studies.Second, the presence of three additional aminoacyltRNA synthetases in the Megavirus genome, with a total of seven, definitely rules out their independent acquisition by lateral transfer from a host. In addition, the phylogenic analysis of their amino acid sequences does not cluster them with any known protozoan clade, but rather connect them deeply to eukaryotic domain.
The conclusion then becomes inescapable that the genome of these giant viruses originated from an ancestral cellular genome (thus endowed of a translation apparatus, with all 20 aminoacyl tRNA synthetases) from which today’s Megaviridae derived by a number of lineage specific genome reduction events, a scenario akin to the one followed by all parasitic organisms. As indicated by the deep rooting of their phylogeny, the Megaviridae lineage might be very old, eventually predating the emergence of modern eukaryotes, or be contemporary and/or linked to the emergence of the nucleus. 5 Alternatively, it could be derived from an extinct cellular domain (the controversial 4th domain of the Tree of Life), many genes of which would have managed to persist in today’s giant viral genomes.
Table1 : Largest giant viruses with complete sequenced genomes
| Giant virus name | Genome Length | Genes | Capsid diameter (nm) | Hair cover | Genbank # |
|---|---|---|---|---|---|
| Megavirus chilensis | 1,259,197 | 1120 proteins (predicted) | 440 | yes (75nm) | JN258408 |
| Mamavirus | 1,191,693 | 1023 proteins (predicted) | 390 | Yes (120 nm) | JF801956 |
| Mimivirus | 1,181,549 | 979 proteins 39 non-coding | 390 | Yes (120 nm) | NC_014649 |
| M4 (Mimivirus « bald » variant) | 981,813 | 756 proteins (predicted) | 390 | No | JN036606 |
| Cafeteria roenbergensis virus | 617,453 (730 kb) | 544 proteins (predicted) | 300 | No | NC_014637 |
Table 2: Specific common features among giant viruses
| Giant virus name | Aminoacyl-tRNA synthetase | Octocoral-like MutS | Stargate | Known virophage | Cytoplasmic virion factory | Host |
|---|---|---|---|---|---|---|
| Megavirus chilensis | 7 (Tyr, Arg, Met, Cys, Trp, Asn, Ile) | yes | yes | no | yes | Acanthamoeba (Unikonta, Amoebozoa) |
| Mamavirus | 4 (Tyr, Arg, Met, Cys) | yes | yes | yes | yes | Acanthamoeba (Unikonta, Amoebozoa) |
| Mimivirus | 4 (Tyr, Arg, Met, Cys) | yes | yes | yes | yes | Acanthamoeba (Unikonta, Amoebozoa) |
| M4 (Mimivirus « bald » variant) | 2 (Met, Cys) | no | yes | resistant | yes | Acanthamoeba (Unikonta, Amoebozoa) |
| Cafeteria roenbergensis virus | 1 (Ile) | yes | no | yes | yes | Phagotrophic protozoan (Heterokonta, Stramenopiles) |
See also
- MimivirusMimivirusMimivirus is a viral genus containing a single identified species named Acanthamoeba polyphaga mimivirus , or is a group of phylogenetically related large viruses . In colloquial speech, APMV is more commonly referred to as just “mimivirus”...
– the giant virus that revolutionized virology - Cafeteria roenbergensis virusCafeteria roenbergensis virusCafeteria roenbergensis virus is a giant virus that infects the marine zooplankton Cafeteria roenbergensis . CroV has the largest genome of any known marine virus, consisting of ~730,000 base pairs of double-stranded DNA...
- the largest marine virus - Papilloma virusParvovirusParvovirus, often truncated to "parvo", is both the common name in English casually applied to all the viruses in the Parvoviridae taxonomic family, and also the taxonomic name of the Parvovirus genus within the Parvoviridae family...
– smallest known single stranded DNA virusesVirusA virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
External links
- GiantVirus.org – an information resource on the genome of giant viruses.
- International Committee on Taxonomy of Viruses (ICTV) picture gallery - images of mimivirus