the_scientist by changcheng2


									Volume 25 | Issue 3 | Page 58
Date: 2011-03-01

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By Richard P. Grant

Come Inside

Lesley McKeane, MRC Visual Aids (virus)

The paper

D.L. Mallery et al., “Antibodies mediate intracellular immunity through tripartite motif-
containing 21 (TRIM21),” PNAS, 107:19985-90, 2010. Free F1000 Evaluation

The finding

Antibodies work by activating the complement cascade, preventing invading microorganisms
from entering cells, or binding to a pathogen and marking it for destruction by immune cells.
Now, Leo James and colleagues at the MRC-LMB in Cambridge have discovered a fourth method
that works inside cells, providing a “last line of defense” against infection.

The ambush

James’ lab observed that antibodies can remain bound to adenovirus as it infects cells. The
result sparked their curiosity, because they had previously shown that the intracellular protein
TRIM21 binds to the F region of antibodies with higher affinity than any other antibody

receptor in the body.

Animated Immunity
Watch antibodies neutralize viral invaders in this animation from the lab of Leo James
Credit: Lesley McKeane, MRC Visual Aids

The neutralization

They found that TRIM21 adds ubiquitin to the adenovirus-antibody complex, targeting it for
destruction by the proteasome. The finding “adds conceptually to the immune response,” says
F1000 Member David Alpers.

The patents

TRIM21 only works if the virus doesn’t shed the antibody as it enters the cell. This means it
should be effective against all nonenveloped viruses, such as rotaviruses and noroviruses,
which cause diarrhea and gastroenteritis. James’ lab is in the process of cataloging which
infections retain antibodies, and looking for other TRIM21-like proteins. They are also trying to
develop novel antiviral therapies, having already applied for patents covering the use of
synthetic TRIM21 to treat infections.

F1000 evaluators: L. Walter (German Primate Center) • D. Alpers (WUSM) • N. Vigneron & B. Van den Eynde (Ludwig Inst for Cancer Res) • G. Versteeg & A. Garcia-Sastre (Mount

Sinai Sch of Med) • D. Koch & N. Sawtell (Cincinnati Children’s Hosp Med Cen)


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Comment on this article

Epigenetics: A Long Overdue Pre-Primer
by Dov Henis

[Comment posted 2011-03-03 07:54:00]
Epigenetics: A Long Overdue Pre-Primer
[Comment posted 2011-03-01]

Science Should Adjust Its Vision, Comprehension And Concepts

From "Think Again: Education" , comment "Science In A Technology-Tradeunion Culture?"

Genes And Genomes Are Both Organisms

Genomes Are RNA-Evolved Template ORGANISMS

EpiDNAtics Is Not Epigenetics

From "Dispel Some Figments Of 2010 Science Imagination"

The "heritable or enduring changes" are epiDNAtics, not epigenetics. Alternative splicing is
not epigenetics, even if/when not involving alteration of the DNA sequence. Earth life is an
RNA world.

It's the RNAs that evolve proteins. AND IT'S THE RNAs THAT HAVE EVOLVED AND
PRODUCE AND EMPLOY THE RNA and (stabler) DNA template genome organisms for
carrying out life processes, i.e. for enhancing Earth's biosphere by proliferating RNAs, for
augmenting and constraining as long as possible some energy by augmenting its, RNA's, self-
propagation, constraining temporarily some of the total energy of the universe, all of which is
nevertheless destined to fuel the ongoing cosmic expansion.

Science should adjust its vision, comprehension and concepts.

Dov Henis
(comments from 22nd century)
Seed of Human-Chimp Genomes Diversity
03.2010 Updated Life Manifest

Read more: Come Inside - The Scientist - Magazine of the Life Sciences http://www.the-

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