virology blog
About viruses and viral disease
The TWiVirions reveal bacteriophage genes that control eukaryotic reproduction, and the biochemical basis for increased Ebolavirus glycoprotein activity during the recent outbreak.
You can find TWiV #431 at microbe.tv/twiv, or listen below.
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The obligate intracellular bacteria Wolbachia (pictured), which infects 40% of arthropods, can manipulate its host to ensure its maintenance in the population. An example is cytoplasmic incompatibility, which occurs when infected males mate with uninfected females, and causes embryonic lethality (mating with an infected female produces viable offspring). Two Wolbachia genes responsible for this phenotype have been identified, and they are viral (link to paper).
A comparison of genome sequences of different Wolbachia strains that do or do not cause cytoplasmic incompatibility (CI) revealed two genes that were candidates for this phenotype. Both genes are transcribed in the testes of fruit flies, but at lower levels in older male flies which show decreased CI.
When either gene was expressed in male transgenic fruit flies, there was no effect on hatch rates after mating with uninfected females. When both genes were expressed in male flies, mating with uninfected females led to substantially reduced hatch rates. This transgene-induced lethality was rescued when the flies were mated with Wolbachia-infected females.
The two genes that together cause CI are called cytoplasmic incompatibility factor A and B (cifA, cifB). The cytological defects caused by these genes resemble those observed in Wolbachia-induced CI: most embryos do not divide more than two or three times.
Remarkably (or perhaps not!), cifA and cifB are not Wolbachia genes, but are viral. Wolbachia are infected with a bacteriophage called WO; nearly all sequenced Wolbachia genomes contain integrated WO DNA, and it is within this WO prophage that are found cifA and cifB. In other words, the ability of Wolbachia to control the reproduction of its arthropod host is regulated by two viral genes integrated in the bacterial genome.
Because CI caused by Wolbachia is a means of increasing their proportion in the female line (the bacteria are maternally inherited), cifA and cifB also enable spread of WO bacteriophage.
How cifA and cifB cause CI is unknown – most of the encoded proteins have no recognized protein domains with the exception of weak homology to proteases.  Understanding this mechanism might also contribute to controlling the spread of arboviruses: Wolbachia is known to inhibit replication of some mosquito borne viruses such as dengue virus and Zika virus.
The TWiVrific gang reveal how integration of a virophage into the nuclear genome of a marine protozoan enhances host survival after infection with a giant virus.
You can find TWiV #419 at microbe.tv/twiv, or listen below.
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Virophages (the name means virus eater) were first discovered to replicate only in amoeba infected with the giant mimiviruses or mamaviruses.  They reduce yields of the giant viruses, and also decrease killing of the host cell. Another virophage called mavirus has been found to integrate into the genome of its host and behaves like an inducible antiviral defense system (link to paper).
The host cell of the virophage mavirus is Cafeteria roenbergensis, Cro (pictured), a marine phagotropic flagellate, that is infected with the giant virus CroV (Cafeteria roenbergensis virus). When Cro cells are infected with a mixture of mavirus and CroV, the virophage integrates into the host cell genome. There it remains silent; the cells survive, and no virophage particles are produced. Such cells can be called lysogens, a name applied to bacteria containing integrated bacteriophage genomes, or prophages.
How does the mavirus genome integrate into the Cro cell? The viral genome encodes an integrase, an enzyme that cuts host DNA and inserts a copy of the viral genome. Retroviruses achieve the same feat via an integrase.
When Cro-mavirus lysogens are infected with CroV, the integrated mavirus genome is transcribed to RNA, the viral DNA replicates, and new virus particles are formed. These virophages inhibit the replication of CroV by 100-1000 fold. As a consequence, the host cell population survives.
These findings suggest that the virophage mavirus is altruistic: induction of the integrated genome leads to killing of the host cell, but other members of the cell population are protected. Altruism is not unknown in Nature, but how it evolved is an intriguing question.
All this work was done in a laboratory. It will be necessary to determine if integration of mavirus into Cro cells in the wild has any influence on the ecology of these organisms.