511-B 4 FEBRUARY 2022 • VOL 375 ISSUE 6580 science.org SCIENCE
RESEARCH
CORONAVIRUS
The unknowns of
an antiviral strategy
Broad antiviral drugs are
needed to target RNA viruses,
including severe acute respira-
tory syndrome coronavirus-2
(SARS-CoV-2), Zika virus, and
Chikungunya virus, which have
caused numerous epidem-
ics. Lethal mutagenesis is an
antiviral strategy whereby drugs
form mutagenic ribonucleosides
in host cells that are used in
viral RNA genome replication,
resulting in enough mutations
to inactivate a replicating virus
and thereby limit infection. The
antiviral drug molnupiravir is
designed to work in this manner
and has recently been approved
for the treatment of COVID-19.
In a Perspective, Swanstrom and
Schinazi discuss the potential
risks of this antiviral approach,
including the possibility of
producing variants and the
potential for host DNA mutagen-
esis. The potential for long-term
effects suggests that safety
assessments of mutagenic
drugs should be examined more
closely. —GKA
Science, abn0048, this issue p. 497
CHEMICAL POLLUTION
Living with forever
chemicals
Per- and polyfluoroalkyl sub-
stances (PFAS) are products of
the modern chemical industry
that have been enthusiastically
incorporated into both essen-
tial and convenience products.
Such molecules, containing fully
fluorine-substituted methyl or
methylene groups, will persist
on geologic time scales and can
bioaccumulate to toxic levels.
Evich et al. review the sources,
transport, degradation, and
toxicological implications of
environmental PFAS. Despite
their grouping together, these
compounds are heterogeneous
in chemical structure, properties,
transformation pathways, and
biological effects. Remediation
is possible but expensive and
is complicated by dispersion in
soil, water, and air. It is important
that we thoroughly investigate
the properties of potential
replacements, many of which are
merely different kinds of PFAS,
and work to mitigate the harms
of the most toxic forms already
released. —MAF
Science, abg9065, this issue p. 512I M M U N O L O GY
Probing human T cell
function using CRISPR
CRISPR activation (CRISPRa)
and CRISPR interference
(CRISPRi) screens are powerful
tools to test the gain and loss of
gene function, but their use has
largely been limited to immor-
talized cell lines. Schmidt et al.
report an optimized method
that allowed them to perform
genome-wide CRISPRa and
CRISPRi screens on primary
human T cells. This approach
was then used to scrutinize
genes regulating the production
of key therapeutically relevant
cytokines. The combination of
pooled CRISPRa perturbations
with single-cell RNA sequenc-
ing (CRISPRa Perturb-seq) then
allowed them to interrogate
how the regulators of cytokine
production can control T cell
activation and programming into
distinct postactivation states.
—STS
Science, abj4008, this issue p. 513PLANT SCIENCE
A volatile defense
against leafhoppers
In established ecosystems,
plants often fend off their
insect attackers using chemi-
cal defenses that are elicited by
herbivore wounding. Some of
these same insects are pests
in the agricultural setting as
well, attacking plants that have
not benefited from chemical
defenses evolved over the ages.Bai et al. leveraged genetic
diversity in a population of
Nicotiana attenuata plants that
they grew in the plant’s native
habitat in Arizona to study how
their chemical defenses provide
resistance to the herbivorous
leafhoppers. A multi-omics
approach led to the identifica-
tion of a volatile compound from
leaves that confers resistance to
those leafhoppers. —PJH
Science, abm2948, this issue p. 514MOLECULAR BIOLOGY
Reassessment of DNA
6mA in eukaryotes
Certain forms of chemical
modifications to DNA play
important roles across the
kingdoms of life; some forms
have been widely studied and
others are relatively new. DNA
N^6 -methyldeoxyadenosine
(6mA), which was recently
reported to be prevalent across
eukaryotes, has created excite-
ment as a target to study in
biology and diseases. However,
some studies have highlighted
confounding factors, and there
is an active debate over 6mA in
eukaryotes. Kong et al. describe
a method for quantitative 6mA
deconvolution and report that
bacterial contamination explains
the vast majority of 6mA in
DNA samples from insects and
plants. The method also found
no evidence for high 6mA levels
in humans (see the Perspective
by Boulias and Greer). This work
advocates for a reassessment of
6mA in eukaryotes and provides
an actionable approach. —DJ
Science, abe7489, this issue p. 515;
see also abn6514, p. 494QUANTUM GASES
Characterizing
second sound
Heat usually propagates
diffusively, but it can also under
certain circumstances propagate
like a wave, much as sound does.
This phenomenon, called secondsound, has been observed in
superfluids, including helium and
ultracold atomic gases. However,
measuring the attenuation of
second sound remains tricky. Li
et al. accomplished this feat by
creating a uniform ultracold gas
of strongly interacting fermionic
lithium atoms with a very large
Fermi energy. Placing the gas in
an external periodic potential
and measuring the response, the
researchers extracted the coef-
ficients characterizing second
sound attenuation. —JS
Science, abi4480, this issue p. 528EMERGING COMPUTING
Reconfigurable
neuromorphic functions
Having all the core functionality
required for neuromorphic com-
puting in one type of a device
could offer dramatic improve-
ments to emerging computing
architectures and brain-inspired
hardware for artificial intel-
ligence. Zhang et al. showed
that proton-doped perovskite
neodymium nickelate (NdNiO 3 )
could be reconfigured at room
temperature by simple electrical
pulses to generate the different
functions of neuron, synapse,
resistor, and capacitor (see
the Perspective by John). The
authors designed a prototype
experimental network that not
only demonstrated electrical
reconfiguration of the device, but
also showed that such dynamic
networks enabled a better
approximation of the dataset for
incremental learning scenarios
compared with static networks.
—YS
Science, abj7943, this issue p. 533;
see also abn6196, p. 495HIV
Evolving virulence in HIV
Changes in viral load and CD4+ T
cell decline are expected signals
of HIV evolution. By examining
data from well-characterized
European cohorts, Wymant et al.
report an exceptionally virulentEdited by Michael FunkALSO IN SCIENCE JOURNALS