LEED screen LEED screen A B
Sample Sample Electron pulse
an earlier study indicated that a bottleneck
selecting for reduced glycosylation of the
virion surface Env protein is also stronger
in female-to-male transmission (5).
That the fitness bottleneck observed in
female-to-male transmission is more severe, but can be reduced by viral load and/
or GUI, suggests that barriers to infection
of the first cell may reduce transmission in
males compared to females. The exposed
surface area of epithelium and/or the density of target cells in or just beneath the
epithelium in the male versus the female
genital tract may be sufficient to explain
this difference, but the ability to spread after infection of the initial cell may also be
selected (see the figure). The transmitted
virus is well adapted to entering cells with
a high density of its receptor CD4 (5–7),
making CD4+ T cells the most likely target,
although the virus can infect macrophages
less efficiently (6, 8, 9). Examination of vaginal tissue in macaques after exposure to the
related virus SIV showed that resting CD4+
T cells are the predominant infected cells,
but infected activated CD4+ T cells are also
observed (10). A paucity of CD4+ T cells in
genital tract tissue could be sufficient to define the low probability of the first infected
cell both being infected and then passing virus on to the next cell. It has been suggested
that a local innate immune response generates type 1 interferon, a cytokine that can
limit viral replication (11, 12). Whether the
selection for fitness is due to low target cell
density, a local innate immune response, or
both is not known.
This new view of HIV-1 transmission suggests that there may be more initial infectious events than infections that become
systemic (R0 << 1). There are exposures of
target cells to virus that fail to initiate an infection, and there is spread of virus from the
initially infected cell(s) that fails to become
a systemic infection, collectively adding a
bias to the distribution of polymorphisms in
the transmitted/founder virus population.
Thus, there is a period during transmission
of a low R0 that HIV-1 must navigate in the
new host to initiate a successful infection. ■
1. J. M. Carlson et al ., Science 345, 1254031 (2014).
2. B. F. Keele etal ., Proc.Natl.Acad.Sci.U.S.A. 105, 7552
3. M.R.Abrahams etal.J.Virol. 83,3556(2009).
4. R. M. Ribeiroetal ., J.Virol. 84, 6096 (2010).
5. L. H. Ping etal., J.Virol. 87, 7218 (2013).
6. S.B.Joseph etal., J.Virol. 88,1858(2014).
7. N. F. Parrish et al ., PLOS Pathog. 8, e1002686 (2012).
8. J. Isaacman-Beck etal ., J.Virol. 83, 8208 (2009).
9. C. Ochsenbauer etal ., J.Virol. 86, 2715 (2012).
10. A. T. Haase, Nature 464, 217 (2010).
11. A. E. Fenton-May et al ., Retrovirology 10, 146 (2013).
12. N. F. Parrish et al ., Proc. Natl. Acad. Sci. U.S.A. 110, 6626
Low-energy electron diffraction (LEED) has been used to determine the sur- face structure of crystalline materials because the diffracted electrons only probe the top atomic layers. First re- ported by Davisson and Germer in
1927 (1), the LEED technique became widely
used when ultrahigh vacuum techniques
introduced in the 1960s allowed surfaces
to remain relatively free from adsorbed
background gases during a typical experiment. However, the information LEED provides about the relative ordering of atoms
on a surface, whether at atomic resolution
or on a larger mesoscopic scale, can only
be understood in a time-averaged, quasi-stationary manner. Dynamical aspects, such
as changes with temperature, have been
only grasped indirectly with well-developed
theoretical models to describe the averaged measured quantities. Time-resolved
monitoring of LEED patterns would enable direct visualization of lattice motions
or light-induced ultrafast phase transitions.
On page 200 of this issue, Gulde et al. (2)
report an ultrafast implementation of LEED
and have resolved the ultrafast melting of a
poly(methylmethacrylate) (PMMA) layer adsorbed to a graphene substrate.
In LEED, electrons are generated at a cathode, accelerated, and focused by electrodes
into an electron beam pointing to the sample
of interest. The diffracted electrons are then
usually detected in reflection using phosphorescent screens (see the figure, panel A.).
Gulde et al. achieved time resolution in
the picosecond regime with a pump-probe
configuration in their transmission ultrafast
LEED (T-ULEED) experiment. An ultrashort
laser pump pulse heats up the PMMA layer,
and the structural changes resulting from
the melting process are monitored as a function of time delay by probing its diffraction
patterns (distinct from those of graphene)
with electron pulses lasting a few picoseconds (see the figure, panel B). The electron
pulses are generated from a sharp tungsten
tip (50-nm radius of curvature) by illumination with a second-harmonic pulse originating from the same laser output as the laser
pump pulse. This method ensures accurate
timing (time delay t) between the two pulses.
The PMMA layer on graphene consists of
three domains of two-dimensional folded
Forward with LEED. (A) Conventional LEED works by reflecting electrons back to a phosphor screen. (B) Time-resolved
LEED described by Gulde et al. uses forward scattering in transmission of electron pulses generated by photoemission.
By Erik T. J. Nibbering
Max Born Institut für Nichtlineare Optik und
Kurzzeitspektroskopie, Max Born Strasse 2A, 12489 Berlin,
Germany. E-mail: firstname.lastname@example.org
diffraction at ultrafast speeds
Thermally induced structural changes in a thin polymer
film could be resolved with picosecond time resolution