Resolving the “tree of life” is among the most interesting and challenging questions in evolutionary biology. Although it is widely held that the Archaea, Bacteria and Eukarya form three distinct domains of life, two competing hypotheses place the Eukaryotes either as a sister taxon to the Archaea – the so-called 3 domains tree. The small genomes of viruses did not contain enough information to reliably position them on the tree of life. This was changed by the discovery of Mimivirus, a nucleocytoplasmic large DNA virus (NCLDV) with a genome of unprecedented size (1.2 Mb) and coding capacity (1,000 ORFs), exceeding that of many cellular organisms. In an initial phylogenetic analysis, Mimivirus emerged from the branch joining Archaea and Eukaryotes, suggesting that it might represent a distinct fourth domain of life. New analysis suggests that the informational genes of NCLDV (RNAP2, PCNA, FEN and TFIIB) have been acquired by horizontal transfer from donors within the eukaryotic domain, and suggests that invoking an ancient “4th domain” for NCLDV, or a special primordial role for NCLDV in the formation of Eukaryotes, are not needed to explain the available molecular sequence data for this group of viruses.
Informational Gene Phylogenies Do Not Support a Fourth Domain of Life for Nucleocytoplasmic Large DNA Viruses. PLoS ONE 6(6): e21080. doi:10.1371/journal.pone.0021080
Mimivirus is a nucleocytoplasmic large DNA virus (NCLDV) with a genome size (1.2 Mb) and coding capacity ( 1000 genes) comparable to that of some cellular organisms. Unlike other viruses, Mimivirus and its NCLDV relatives encode homologs of broadly conserved informational genes found in Bacteria, Archaea, and Eukaryotes, raising the possibility that they could be placed on the tree of life. A recent phylogenetic analysis of these genes showed the NCLDVs emerging as a monophyletic group branching between Eukaryotes and Archaea. These trees were interpreted as evidence for an independent “fourth domain” of life that may have contributed DNA processing genes to the ancestral eukaryote. However, the analysis of ancient evolutionary events is challenging, and tree reconstruction is susceptible to bias resulting from non-phylogenetic signals in the data. These include compositional heterogeneity and homoplasy, which can lead to the spurious grouping of compositionally-similar or fast-evolving sequences. Here, we show that these informational gene alignments contain both significant compositional heterogeneity and homoplasy, which were not adequately modelled in the original analysis. When we use more realistic evolutionary models that better fit the data, the resulting trees are unable to reject a simple null hypothesis in which these informational genes, like many other NCLDV genes, were acquired by horizontal transfer from eukaryotic hosts. Our results suggest that a fourth domain is not required to explain the available sequence data.
Closely related to this comes the news that in the absence of competition with other microorganisms, Mimivirus, the largest known DNA virus, loses 17% of its genome. In a natural environment Mimiviruses live in a “community.” They share their amoebal hosts with other organisms such as viruses and bacteria. Constant exchanges of genes within these organisms with intra-amoebal life, not just between each other but also with their protozoan host, have allowed this evolution towards a “community” life. Researchers cultivated Mimivirus in the laboratory, alone in an amoeba without contact with other organisms. After only 150 passages, they observed a 17% reduction in the size of its genome. This genomic loss mainly occurs in the form of deletions of both ends of the genome. In the absence of other microorganisms and thus competition within the host, the Mimivirus eliminates part of its genome by deleting in particular the genes involved in the formation of the long fibers that surround its capsid, becoming “bald.” The researchers also found that this deleted form became resistant to virophages.
Mimivirus shows dramatic genome reduction after intraamoebal culture. (2011) PNAS USA 108(25): 10296-10301 doi: 10.1073/pnas.1101118108
Most phagocytic protist viruses have large particles and genomes as well as many laterally acquired genes that may be associated with a sympatric intracellular life (a community-associated lifestyle with viruses, bacteria, and eukaryotes) and the presence of virophages. By subculturing Mimivirus 150 times in a germ-free amoebal host, we observed the emergence of a bald form of the virus that lacked surface fibers and replicated in a morphologically different type of viral factory. When studying a 0.40-μm filtered cloned particle, we found that its genome size shifted from 1.2 (M1) to 0.993 Mb (M4), mainly due to large deletions occurring at both ends of the genome. Some of the lost genes are encoding enzymes required for posttranslational modification of the structural viral proteins, such as glycosyltransferases and ankyrin repeat proteins. Proteomic analysis allowed identification of three proteins, probably required for the assembly of virus fibers. The genes for two of these were found to be deleted from the M4 virus genome. The proteins associated with fibers are highly antigenic and can be recognized by mouse and human antimimivirus antibodies. In addition, the bald strain (M4) was not able to propagate the sputnik virophage. Overall, the Mimivirus transition from a sympatric to an allopatric lifestyle was associated with a stepwise genome reduction and the production of a predominantly bald virophage resistant strain. The new axenic ecosystem allowed the allopatric Mimivirus to lose unnecessary genes that might be involved in the control of competitors.
The main impediment to a cure for HIV is the existence of long-lasting treatment resistant virus reservoirs. This review discusses what is currently known about reservoirs, including their formation and maintenance, while focusing on latently infected CD4+ T cells. It compares several different in vivo and in vitro models of latency and comments on how each model may reflect the properties of reservoirs in vivo, especially with regard to cell phenotype, since recent studies demonstrate that multiple CD4+ T cell subsets contribute to HIV reservoirs and that with HAART and disease progression the relative contribution of different subsets may change. It also focuses on the direct infection of resting CD4+ T cells as a source of reservoir formation and as a model of latency, since recent results help explain the misconception that resting CD4+ T cells appeared to be resistant to HIV in vitro.
Viruses exploit host cells for their propagation. Once an adequate number of virus particles have been assembled, they must be released from the cell for the virus to spread. For nonenveloped viruses or viruses that are solely encapsulated by a protein shell, this step most commonly involves the perforation of cellular membranes resulting in the lysis or death of the host cell. The mechanism for how this key terminal step in the viral life cycle is performed is poorly understood. For the model nonenveloped virus SV40, the newly discovered virus-encoded protein, VP4, perforates membranes by forming pores with a diameter of ~3 nm in host cell membranes. While these pores are not of a sufficient size to provide a conduit that permits the movement of the virus through the membrane, they support membrane destabilization that leads to the disintegration of the membrane of the host cell and virus release, actin as a 
