Curing infected cells instead of killing them

Once a cell is infected, our immune system clears the infection not by targeting the virus, but by simply killing the infected cell.  Antibodies are also an important part of our defense against viral infections, but their function is limited to targeting viruses floating around outside the cell.  It is believed the once the virus enters the cell, it’s safe from antibodies.  But a recent study suggests that this may not be true; it seems that antibodies can eliminate viruses from inside cells too.  This is particularly groundbreaking because this may be a mechanism to cure infected cells, rather than just killing them.

Researchers identified a protein called TRIM21 that binds antibodies, but it was localized to the cell’s cytoplasm.  Why would it be there, when antibodies are secreted?  It seems that sometimes viruses can enter a cell with antibodies bound to it.  While some antibodies are neutralizing, meaning that they prevent attachment to the receptor, others are not.  If the virus is coated with these non-neutralizing antibodies, it can still enter, and it bring the antibodies in with it.  TRIM21 recognizes these internalized antibodies, with virions attached to them, and then targets it for destruction in a cellular blender called the proteasome. In an appropriately named “fate of capsid” experiment, the researchers showed that antibody bound adenovirus capsid proteins were being degraded as soon as 2 hours after infection and that the degradation required both the proteasome and TRIM21.  So the virus is being destroyed quickly, before it gets the chance to replicate.

As always, this study introduces many new questions.  They used adenovirus, which causes mild respiratory infections, but does the mechanism extend to other non-enveloped viruses? Can this mechanism be used to improve existing vaccines or develop new ones? How important is this mechanism in the overall response to viral infection?  Have viruses evolved mechanisms to block TRIM21?

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Frank Fenner 1914-2010

It is with great sadness that I report the death of one of my science heroes, Frank Fenner. One of the key people involved in the eradication of smallpox, he was also a prolific researcher in poxvivrology, and discoverer of the virus I study, ectromelia virus. Although I never met him, I have read many of his papers and they have influenced my own research and interests.

Here is the text of the email I received this morning, from Julio Lincio:

“Frank John Fenner AC, CMG, MBE, FRS, FAA (born 21 December 1914,died 22 November 2010) was an Australian scientist with a distinguished career in the field of virology. His two greatest achievements are cited as overseeing the eradication of smallpox during his term as Chairman of the Global Commission for the Certification of Smallpox Eradication, and the control of Australia’s rabbit plague through the introduction of myxoma virus.

Professor Fenner was Director of the John Curtin School from 1967 to 1973. During this time he was also Chairman of the Global Commission for the Certification of Smallpox Eradication. In 1973 Professor Fenner was appointed to set up the new Centre for Resource and Environmental Studies at the Australian National University (ANU). He held the position of Director until 1979.

Professor Fenner has been elected a fellow of numerous faculties and academies, including Foundation Fellow of the Australian Academy of Science (1954), Fellow of the Royal Society (1958), and Foreign Associate of the United States National Academy of Sciences (1977).

During his career Professor Fenner received many awards. Among these are the Britannica Australia Award for Medicine (1967), the Australia and New Zealand Association for the Advancement of Science Medal (1980), the World Health Organization Medal (1988), the Japan Prize (1988), the Senior Australian Achiever of the Year (1999), the Albert Einstein World Award for Science (2000), and the Prime Minister’s Science Prize (2002).

A man of decisive scientific action and strong opinions, Professor
Fenner’s last interview with The Australian is extremely thought provoking and can be found here

A summary of Frank’s remarkable career can be found here

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