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very remote (high-redshift) SNe Ia.
Perlmutter’s team has met this challenge
by developing a search strategy that virtually
guarantees the discovery of batches of high-
redshift (z > 0.3) SNe Ia during an observing
run at a large ground-based telescope5. The
guarantee means that coordinated observa-
tions by other telescopes can be arranged in
advance.
In this issue, Perlmutter et al.1 present
observations of SN1997ap, at the very high
redshift z = 0.83. (The Universe has expand-
ed since then by a factor of 1.83.) The bright-
ness against time of SN1997ap was measured
from the ground and from the Hubble Space
Telescope, and the Keck telescope con-
tributed a good spectrum to prove that it was
a normal type Ia. The data do not support VM
= 1. A rival pack of high-redshift-supernova
hunters6 has also tentatively concluded that
VM is low. So if space is flat, there must be a
cosmological constant.
The prospects for more precisely measur-
ing VM and VL are bright. Both groups
already have data on dozens of remote SNe
Ia, including a number near z = 1; these will
provide the leverage needed to determine VM
and VL separately7. Astronomers will be
wondering whether these analyses could be
underestimating VM. The inferred value
Kaposi’s sarcoma
Coupling herpesvirus
to angiogenesis
Chris Boshoff
ince the discovery of Kaposi’s sarcoma-
would come out higher if remote SNe Ia were
observed to be brighter than they are, relative
to low-redshift supernovae. Could the high-
redshift SNe Ia of the younger Universe be
intrinsically dimmer than the nearer ones?
(Not likely, if they have normal spectra.)
Could there be wavelength-neutral inter-
galactic obscuration? Could the low-redshift
sample be seriously biased by observational
selection effects?
8
If the answers to these and other such
questions prove to be no, it will become
clear that expansion is here to stay. We should
keep in mind, though, that if the cosmological
principle (large-scale homogeneity) isn’t
valid, we could simply be exploring the
nature and future of just one bubble in a
cosmic sea of champagne.
David Branch is in the Department of Physics and
Astronomy, University of Oklahoma, Norman,
Oklahoma 73019, USA.
e-mail: branch@phyast.nhn.yoknar.edu Figure 1 Kaposi’s sarcoma biopsy. a, Numerous
1. Perlmutter, S. et al. Nature 391, 51–54 (1998). vascular spaces and extravasated red blood cells
2. Carroll, S. M., Press, W. H. & Turner, E. L. Annu. Rev. Astron. are surrounded by spindle (‘tumour’) cells.
Astrophys. 30, 499–542 (1992).
3. Ruiz-Lapuente, P., Canal, R. & Isern, J. (eds) Thermonuclear
b, Higher magnification of spindle cells, showing
Supernovae (Kluwer, Dordrecht, 1997). abundant magenta staining for the powerful
4. Saha, A. et al. Astrophys. J. 486, 1–20 (1997). angiogenic protein, vascular endothelial growth
5. Perlmutter, S. et al. Astrophys. J. 483, 565–581 (1997).
6. Garnavich, P. et al. Astrophys. J. (in the press).
factor. (Reproduced, with permission, from ref. 2.)
7. Goobar, A. & Perlmutter, S. Astrophys. J. 450, 14–18
(1995). GPCRs, KSHV-GPCR is fully active in the
absence of chemokine ligands4. Bais et al.3
show that KSHV-GPCR can, indeed, act as a
viral oncogene to transform NIH3T3 cells,
and that this transformation is accompanied
by secretion of VEGF. Spindle cells in Kaposi’s
sarcoma belong to the endothelial lineage, but
they often express antigens characteristic of
endothelial, macrophage and smooth-muscle
cells. This indicates that they either represent
erful angiogenic agent called vascular pluripotent mesenchymal precursors, or are

S associated herpesvirus (KSHV) only

three years ago1, and its detection in
every Kaposi’s sarcoma biopsy (Fig. 1), there
endothelial growth factor (VEGF)2. Angio-
genesis — the sprouting of new blood vessels
from pre-existing ones — is essential for
endothelial cells undergoing aberrant differ-
entiation. KSHV DNA is present in most spin-
dle cells, and also in endothelial cells and
have been many hypotheses to explain how tumour progression and, on page 86 of this monocytes in Kaposi’s sarcoma lesions.
this virus contributes to the abundant vascu- issue, Bais et al.3 report that the G-protein- The KSHV-GPCR gene is not the only viral
lature and spindle-cell proliferation that are coupled receptor (GPCR) encoded by KSHV oncogene to induce tumour formation and
associated with the disease. Spindle cells are induces an ‘angiogenic switch’ in transformed angiogenesis. Cells transformed by v-Ha-ras
considered to be the ‘tumour’ cells, and they NIH3T3 cells. and v-raf (the constitutively active retroviral
contain (and secrete) large amounts of a pow- Like experimentally mutated cellular forms of cellular ras and raf) express increased
Viral pirates on a cellular sea
KSHV-GPCR is just one of an are probably more recent counterparts, and may even that this is not blocked
extraordinary number of acquisitions from the host be exploited for by the normal cell-cycle
genes that are pirated8,10 genome, and they might development of therapies. control mechanisms.
from eukaryotic cellular DNA support viral replication in a For example, the D-type Similarly, the chemokines
by KSHV. The structural specific microenvironment cyclin encoded by KSHV that are encoded by KSHV
proteins and viral enzymes (which, for KSHV, could be binds to its activating are more promiscuous
that are common to most the microvasculature). cellular partner cyclin- than their cellular
herpesviruses probably The captured eukaryotic dependent kinase 6 (Cdk6). counterparts12. Moreover,
originated from an ancient genes have acquired unique This association seems to the viral chemokines
progenitor of contemporary properties (through be resistant to proteins that induce angiogenesis and
herpesviruses. But the accelerated evolution within inhibit Cdk6 (ref. 11), might, therefore, also be
recognizable cellular genes the viral genome) which can meaning that the KSHV— directly involved in the
occur only sporadically in give us insight into the cyclin D complex can drive pathogenesis of Kaposi’s
some herpesviruses. They biology of their cellular cellular proliferation, and sarcoma12. C.B.

24 Nature © Macmillan Publishers Ltd 1998 NATURE | VOL 391 | 1 JANUARY 1998

Terminal
repeat
K12 71 72
?LMP vFLIP vCyclin
Latent
Latent/lytic
Figure 2 ‘Oncogenic cluster’ in the genome of Kaposi’s sarcoma-associated herpesvirus (KSHV). The
G-protein-coupled receptor (GPCR) is encoded by a viral gene that is transcribed with a homologue of
OX2. Four other viral genes are transcribed in the opposite direction, and from different promoters.
Bais et al.3 have shown that GPCR acts as a viral oncogene, and that cellular transformation is
accompanied by secretion of vascular endothelial growth factor. K12 is a latent membrane protein
(LMP) that may act like one of the latent membrane proteins of Epstein–Barr virus.
VEGF5. But these genes induce a different sig-
nalling pathway from KSHV-GPCR. Bais et al.
have found that GPCR triggers the JNK/SAPK
and p38MAPK pathways, although they have
not shown whether these cascades are
involved in the induction of VEGF. So as many
as three major signalling pathways that link
membrane receptors with the nucleus in
mammalian cells could, potentially, be
involved in tumour progression by switching
on angiogenesis. The viral interferon regula-
tory factor is another KSHV-encoded protein
that can transform NIH3T3 cells and induce
tumour formation in nude mice6.
The KSHV-encoded GPCR is part of a
potential ‘oncogenic cluster’ of proteins
within the viral genome. It is transcribed with
OX2 (S. Talbot, unpublished data), which is a
protein involved in intercellular signalling.
This transcript is in the opposite direction —
and from a different promoter — to three
viral genes (Fig. 2), which encode cyclin D,
vFLIP (viral FLICE inhibitory protein), and
an immunogenic latent nuclear antigen,
LNA-1. The vFLIP protein contains a death-
effector domain, and it is homologous to the
cellular FLIP protein7. Like cellular FLIP,
vFLIP might block one of the main pathways
by which immune mechanisms cause cell
death — induction of apoptosis by the
tumour-necrosis factor family of receptors.
LNA-1 resembles the Epstein–Barr virus
nuclear antigens (EBNAs). It may transacti-
vate other cellular or viral genes to promote
cellular growth or, like EBNA-1, it could
maintain the viral DNA in an extrachromo-
somal circular (episomal) form.
Herpesviral proteins can be classified as
being either ‘latent’ or ‘lytic’. Latent proteins
are expressed during non-replicative infec-
tion, whereas lytic proteins are expressed dur-
ing viral replication, and they are associated
with cell death. In KSHV, the expression pat-
NATURE | VOL 391 | 1 JANUARY 1998
Terminal
repeat
73 K14 74
LNA-1 vOX2 vGPCR
tern of the pirated genes (see box) is more
murky — many genes are expressed during
both the lytic and latent phases, although they
are upregulated during lytic infection8. The
pattern of viral gene expression also seems to
differ in haematopoietic compared with
endothelial cells. For example, KSHV-encod-
ed interleukin-6 is expressed in latently infect-
ed B cells, but not in spindle cells8.
KSHV-GPCR is expressed in latent B cells,
and upregulated with lytic induction. Both
types of KSHV infection are present in
Kaposi’s sarcoma9, and both probably con-
tribute to the complex pathology of the dis-
Low-temperature physics
Condensate forced out of hiding
Allan Griffin
elow a temperature of 2.17 K, liquid
B 4
He undergoes a phase transition to a
new state of matter with superfluid
properties. It has long been accepted that a
Bose–Einstein condensate is responsible,
namely that a macroscopic number of atoms
occupy the same quantum state. Direct evi-
dence for this condensate has eluded our best
efforts for many decades, but finally, as
reported on page 56 of this issue by Wyatt1, a
macroscopic fraction of atoms with zero
momentum has been observed in liquid 4He.
A Bose condensate of Cooper pairs also
underlies superfluidity in superconductors
and liquid 3He.
Wyatt used high-energy phonons gener-
ated in the bulk liquid to knock atoms from
the free surface of superfluid 4He (Fig. 1,
overleaf), and then measured their kinetic
energy and momentum2. In the new
analysis1, Wyatt finds that all the evaporated
atoms initially had zero momentum parallel
Nature © Macmillan Publishers Ltd 1998
news and views
ease. Most spindle cells in Kaposi’s sarcoma
are latently infected, although many might
undergo lytic infection at some point. Lytic
infection, with production of viral particles,
might be necessary to drive the formation of
lesions. It is also possible that ‘abortive lytic’
infection (meaning that most early lytic genes
are expressed) contributes to the formation of
tumours in Kaposi’s sarcoma.
The complex histology and expression
8
pattern of KSHV proteins in Kaposi’s
sarcoma indicate that the model of tumori-
genesis might not be like any other virus-
induced malignancy. The irony of current
KSHV research is that, despite having all
this ammunition to trigger a malignancy,
nobody has yet shown that KSHV can trans-
form any cell type in vitro. Moreover, only a
fraction of immunocompetent infected
patients will actually develop a tumour
associated with this virus.
Chris Boshoff is at the Chester Beatty Laboratories,
Institute of Cancer Research, 237 Fulham Road,
London SW3 6JB, UK.
e-mail: cboshoff@icr.ac.uk
1. Chang, Y. et al. Science 266, 1865–1869 (1994).
2. Cornali, E. et al. Am. J. Pathol. 149, 1851–1869 (1996).
3. Bais, C. et al. Nature 391, 86–89 (1998).
4. Arvanitakis, L., Geras-Raaka, E., Varma, A., Gershengorn, M. C.
& Cesarman, E. Nature 385, 347–349 (1997).
5. Grugel, S., Finkenzeller, G., Weindel, K., Barleon, B. & Marme, D.
J. Biol. Chem. 270, 25915–25919 (1995).
6. Gao, S.-J. et al. Oncogene 15, 1979–1985 (1997).
7. Irmler, M. et al. Nature 388, 190–195 (1997).
8. Moore, P. S., Boshoff, C., Weiss, R. A. & Chang, Y. Science 274,
1739–1744 (1996).
9. Orenstein, J. M. et al. AIDS 11, 735–745 (1997).
10. Neipel, F., Albrecht, J.-C. & Fleckenstein, B. J. Virol. 71,
4187–4192 (1997).
11. Swanton, C. et al. Nature 390, 184–187 (1997).
12. Boshoff, C. et al. Science 278, 290–293 (1997).
to the liquid surface. These results end a long
and sometimes controversial search in low-
temperature physics, and development of
the technique opens up the exciting possibil-
ity of producing a phase-coherent beam of
4
He atoms, a kind of ‘atom laser’.
Recalling a little history should make the
significance of these results clear. Within
weeks of the discovery of the superfluid
properties of liquid 4He in 1938, Fritz
London3 suggested that they were a conse-
quence of the fact that 4He atoms have zero
spin, and hence obey Bose statistics. (Bosons
are particles with integer spin 0, 1, 2, …;
fermions have spin 1/2, 3/2, ... .) In particular,
London argued that superfluidity was related
to the occurrence of Bose–Einstein condensa-
tion (BEC) in a liquid, similar to that predict-
ed in an ideal gas a decade earlier by Einstein4
in a paper that had fallen into disfavour. Lon-
don’s colleague Tisza5 quickly developed a
two-fluid model, in which the superfluid
25