Altruistic viruses

Cafeteria roenbergensisVirophages (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.

TWiV 418: Of mice and MERS

The TWiVsters describe a new animal model for MERS coronavirus-induced acute respiratory distress syndrome, produced by CRISPR/Cas9 editing of the mouse gene encoding an ortholog of the virus receptor.

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TWiM 140: Small town, big science

At the Hamilton, Montana Performing Arts Center, Vincent speaks with three local high school graduates and two high school teachers about how Rocky Mountain Laboratories influenced school science programs and opened up career opportunities.

You can find TWiM #140 at microbe.tv/twim, or listen and watch here.

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TWiV Special: Gary Nabel on World AIDS Day 2016

For World AIDS Day 2016, Vincent speaks with Gary Nabel, Chief Scientific Officer at Sanofi and former Director of the Vaccine Research Institute of NIAID, about his career and his work on HIV vaccines.

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TWiV 417: O is the loneliest letter

The Fellowship of the Virus trace the early history of HIV in North America, based on genome sequences obtained from late 1970s archival sera, which also reveal that Gaetan Dugas was not Patient Zero.

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Dugas was not AIDS Patient Zero

aids_index_case_graphThe popular history of HIV/AIDS describes a man known as Patient Zero, a sexually active flight attendant who traveled the globe and initiated the AIDS epidemic in North America. A new analysis of the viral genome recovered from his serum and that of other patients in the 1970s proves beyond a doubt that he was not Patient Zero (link to paper).

In a heroic effort, thousands of archived serum samples originally collected from cohorts of men who have sex with men in the 1970s in New York and San Francisco, were examined for the presence of HIV by western blot analysis. A total of 83 samples were found to be HIV positive and subjected to deep sequencing, but the viral RNA was degraded and present only in short pieces. To overcome this problem, many DNA primers were used to amplify short RNA fragments by PCR in a procedure colorfully called ‘jackhammering’. The impressive result is that complete HIV-1 coding sequences were obtained from 8 samples: 3 from San Francisco and 5 from New York City.

Analysis of the HIV genome sequences, and comparison with earlier and later data revealed that the virus likely traveled from Africa to the Caribbean around 1967, and from there to New York City in 1971. These results disprove previous ideas that HIV arrived in the Caribbean from the US.

Sequence analysis also reveals that New York City was a hub of early diversification of HIV, and that the epidemic was already mature and genetically diverse by the late 1970s. There appears to have been a single introduction of HIV into San Francisco from New York City in 1976. From those two cities the virus spread elsewhere in the US and overseas.

It has been suggested that a sexually active flight attendant, identified as Gaetan Dugas by Randy Shilts in his book And the Band Played On, was the source of the North American AIDS epidemic. Although at least one study years ago concluded that he was not the first case, this belief persists. Sequencing of HIV from this patient’s serum revealed that he was certainly not the first person in North America infected with this line of HIV-1 (Group M, subtype B) .

A historical reconstruction of the early days of AIDS in the US reveals how Dugas earned the label ‘Patient Zero’. CDC investigators who were studying a sexual network of 40 gay men placed one man at its center, whom they called ‘Patient O’, standing for ‘outside of California’ because he was Canadian (pictured; image credit). Upon publication of this work, the ‘O’ was misinterpreted as a zero and so began the belief that he was the origin of the AIDS outbreak in North America.

TWiV 415: Ebola pipettors and the philosopher’s clone

Jeremy Luban, Aaron Lin, and Ted Diehl join the TWiV team to discuss their work on identifying a single amino acid change in the Ebola virus glycoprotein from the West African outbreak that increases infectivity in human cells.

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Zika virus in Nicaragua with Eva Harris

I spoke with Eva Harris of the University of California, Berkeley, on the state of Zika virus in Nicaragua.

Zika in the Guys

In this episode of Virus Watch, we explore the finding that Zika virus infects the testis of mice, causing damage to the organ, reduced sperm production, and less fertility. The important question: does the same happen in humans?

TWiV 414: Zika in the guys with Diamond

On episode #414 of the science show This Week in Virology, Michael Diamond visits the TWiV studio to talk about chikungunya virus and his laboratory’s work on a mouse model of Zika virus, including the recent finding of testicular damage caused by viral replication.

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