Actualité scientifique
Scientific news
N° 483
July 2015
Actualidad científica
How the zika virus infects human cells
When mosquitoes Aedes aegypti and A. albopictus (above) sting in search of a blood vessel, they deposit the virus zika in the dermis and epidermis. (© IRD / M. Dukhan)
Like its cousins the dengue and chikungunya viruses, zika is an emerging
virus. Since the 2007 epidemic in Micronesia which revealed its existence, it
broke out in French Polynesia in late 2013 with 55,000 people affected, and has
now reached Brazil. Researchers from IRD, INSERM (French National Institute
for Health and Medical Research) the Institut Pasteur and their Thai partners
have recently described for the first time how it infects humans following a
mosquito bite and then spreads through the patient. Their discoveries open
the way to developing a treatment.
Key points
Dengue, chikungunya, and the zika virus belong to the group of arboviruses. Originally from Africa, they have emerged in recent
years in several regions around the world. Fever, joint pain, headaches, and cutaneous signs are the most frequently encountered
symptoms. Neurological complications may occur, as in the cases of zika fever in French Polynesia at the end of 2013.
Glossary
Arbovirus: viruses in various families transmitted by blood-sucking arthropods (mosquitoes, ticks, and sand flies) such as the
agents of yellow, dengue, chikungunya and zika fevers.
Dermis: one of the three layers making up the skin, between the hypodermis and the epidermis.
A simulated mosquito bite
Zika is transmitted by Aedes aegypti and
A. albopictus mosquitoes. When the insect
bites a human, its snout probes around
looking for a blood vessel. In doing so,
it deposits virus particles in the victim’s
epidermis and dermis. To simulate infection
in a laboratory, researchers inoculated
a zika virus isolate, collected during the
2013 epidemic in French Polynesia, with
three types of human skin cells, namely
keratinocytes, found in the epidermis, and
fibroblasts and dendritic cells, located in
the dermis. The latter are immune system
cells playing a key role in the production of
appropriate antibodies.
The virus destroys dermis cells to
spread
The result was that 100% of the fibroblasts
were infected within 72 hours. The other
cells were also affected, especially the
keratinocytes. Using electronic imaging,
the researchers demonstrated that
the virus uses autophagy to replicate,
a mechanism consisting of the partial
degradation of cyctoplasm by the cell
itself. This phenomenon eventually leads
to cellular apoptosis, or death by breaking
up, and in this way boosts dissemination
of the pathogenic agent. These reactions
result in the formation of an oedema in the
skin section, which does in fact match one
of the symptoms seen in patients suffering
from zika fever.
Preventing infection
Having confirmed that the virus does in fact
target cutaneous cells, the team identified
the cell receptor enabling the virus to enter
fibroblasts. It is a protein called “AXL”. The
scientists then checked the antibodies’
effectiveness against this protein, together
with small silencing RNAs that suppress
target genes. These fully extinguish this
receptor, thereby blocking infection of the
cell and greatly reducing the rate of cell
infection.
All of this work is a first as regards zika virus
biology. It opens the way to identification of
therapeutic targets to produce a treatment,
which is currently based solely on dealing
with the symptoms.
Coordination
Gaëlle Courcoux
Information and Culture
Department
T. +33 (0)4 91 99 94 90
[email protected]
www.ird.fr/la-mediatheque
Partners
Mahidol University in Thailand, INSERM
(French National Institute for Health and
Medical Research), Institut Pasteur
Work financed by the ANR (French National
Research Agency) as part of the KerARBO and
TIMTAMDEN projects.
References
Hamel Rodolphe, Dejarnac O, Wichit S,
Ekchariyawat P, Neyret A, Luplertlop N, PereraLecoin M, Surasombatpattana P, Talignani L,
Thomas F, Cao-Lormeau VM, Choumet V, Briant
L, Desprès P, Amara A, Yssel H, Missé Dorothée.
Biology of zika virus infection in human skin
cells. Journal of Virology, 2015, pii: JVI.0035415. doi:10.1128/JVI.00354-15
Contacts
Dorothée Missé, IRD researcher
T. +33 (0)4 67 41 63 81
[email protected]
Rodolphe Hamel, PhD student at IRD
[email protected]
UMR Maladies infectieuses et vecteurs :
écologie, génétique, évolution et contrôle MIVEGEC (IRD / CNRS / université Montpellier)
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Media Contact
Cristelle DUOS
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Indigo, IRD Photo Library
Daina Rechner
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© IRD/DIC, Mars 2015 - Conception et réalisation graphique : L. CORSINI
An emerging virus
A newcomer to the arbovirus family, zika is
causing quite a stir. After Micronesia in the
Pacific in 2007, then French Polynesia in
late 2013, it is now affecting Brazil, giving
rise to fears that it will reach the French
West Indies sooner or later. A team of
researchers from IRD, INSERM (French
National Institute for Health and Medical
Research) the Institut Pasteur and their
Thai partners have recently described the
biology of the virus for the first time - how
it infects the host, replicates and spreads.
Contacts