SCIENCE sciencemag.org 4 SEPTEMBER 2020 • VOL 369 ISSUE 6508 1205-C
RESEARCHharmonized protocols, the
researchers found a 29% posi-
tive rate for SARS-CoV-2 among
collected samples. More than
100 international introductions
of SARS-CoV-2 into Brazil were
identified, including three clades
introduced from Europe that
were already well established
before the implementation of
NPIs and travel bans. The virus
spread from urban centers to the
rest of the country, along with a
25% increase in the average dis-
tance traveled by air passengers
before travel bans, despite an
overall drop in short-haul travel.
Unfortunately, the evidence
confirms that current interven-
tions remain insufficient to keep
virus transmission under control
in Brazil. —CA
Science, this issue p. 1255
CORONAVIRUS
A decoy receptor for
SARS-CoV-2
For severe acute respiratory
syndrome coronavirus 2 (SARS-
CoV-2) to enter human cells, the
spike protein on the surface of
the virus must bind to the host
receptor protein, angiotensin-
converting enzyme 2 (ACE2). A
soluble version of the receptor is
being explored as a therapeutic.
Chan et al. used deep mutagene-
sis to identify ACE2 mutants that
bind more tightly to the spike
protein and combined muta-
tions to further increase binding
affinity (see the Perspective by
DeKosky). A promising variant
was engineered to be a stable
dimer that has a binding affin-
ity for the spike protein; it is
comparable with neutralizing
antibodies and neutralized both
SARS-CoV-2 and SARS-CoV-1 in
a cell-based assay. In addition,
the similarity to the natural
receptor may limit the possibility
for viral escape. —VV
Science, this issue p. 1261;
see also p. 1167
NEURODEGENERATION
Unraveling protein
clumping
Repeat expansion in the C9orf72
gene causes amyotrophic lateral
sclerosis (ALS) and fronto-
temporal dementia (FTD), two
neurodegenerative disorders
with common features. A
proportion of patients with ALS
or FTD present cytoplasmatic
aggregates of a protein called
TDP-43 in the brain. The mecha-
nisms mediating the formation
of TDP-43 aggregates are
unclear. Cook et al. now show
that a poly-glycine-arginine
protein (poly-GR) produced by
the repeat expansion enhanced
the formation of TDP-43 aggre-
gates in vitro and in vivo in mice
by altering nucleocytoplasmic
transport. Targeting the repeat
expansion with a specific anti-
sense oligonucleotide reduced
the formati on of TDP-43 aggre-
gates. The results illuminate
the mechanisms mediating the
formation of toxic aggregates
in neurodegenerative diseases.
—MM
Sci. Transl. Med. 12 , eabb3774 (2020).WOUND HEALING
A pain sensor promotes
regeneration
Wound healing in mammalian
skin often results in fibrotic
scars, and the mechanisms by
which original nonfibrotic tissue
architecture can be restored
are not well understood. Wei et
al. found that pharmacological
activation of the pain sen-
sor TRPA1, which is found on
cutaneous sensory neurons,
can limit scar formation and
promote tissue regeneration.
They confirmed the efficacy
of TRPA1 activation in three
different skin-wounding mouse
models and observed that local-
ized activation could generate
a response at distal wound
sites. TRPA1 activation induced
interleukin-23 production by
dermal dendritic cells, which
activated interleukin-17–pro-
ducing gd T cells and promoted
tissue regeneration. These
findings provide insight intoneuroimmune signaling path-
ways in the skin that are critical
to mammalian tissue regenera-
tion. —CNF
Sci. Immunol. 5 , eaba5683 (2020).Published by AAAS