Like its cousins, the dengue and chikungunya viruses, Zika is an emerging virus. It was revealed in the 2007 epidemic in Micronesia and has since hit Polynesia (end 2013) where 55,000 people have been affected. It has now reached Latin American and the Caribbean. For the first time in 2015, researchers from IRD, Inserm, Institut Pasteur and their Thai partners described how it infects humans after a mosquito bite then spreads in the patient. Their discoveries have opened the way for the development of treatment.
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.
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 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.
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.