Abstract
Dengue virus (DENV) is naturally transmitted by mosquitoes to humans, infecting cells of both hosts. Unlike in mammalian cells, DENV usually does not cause extremely deleterious effects on cells of mosquitoes. Despite this, clustered progeny virions were found to form infection foci in a high density cell culture. It is thus interesting to know how the virus spreads among cells in tissues such as the midgut within live mosquitoes. This report demonstrates that cell-to-cell spread is one way for DENV to infect neighboring cells without depending on the “release and entry” mode. In the meantime, a membrane-bound vacuole incorporating tetraspanin C189 was formed in response to DENV infection in the C6/36 cell and was subsequently transported along with the contained virus from one cell to another. Knockdown of C189 in DENV-infected C6/36 cells is shown herein to reduce cell-to-cell transmission of the virus, which may be recovered by co-transfection with a C189-expressing vector in DENV-infected C6/36 cells. Moreover, cell-to-cell transmission usually occurred at the site where the donor cell directly contacts the recipient cell. It suggested that C189 is crucially involved in the intercellular spread of progeny viral particles between mosquito cells. This novel finding presumably accounts for the rapid and efficient infection of DENV after its initial replication within tissues of the mosquito.
Highlights
Dengue virus (DENV) consists of four serotypes that manifest similar symptoms, ranging from a mild febrile illness to a life-threatening dengue hemorrhagic fever [1]
We found that infection of DENV in C6/36 mosquito cells can stimulate the up-regulation of tetraspanin C189, which usually co-localizes but does not directly interact to form C189-containing membrane-bound vacuoles (C189-VCs)
Our results showed that the virus can be delivered to a neighboring cell along with C189-VCs, frequently through cell contact with filopodia extended by the donor cell that touch the PLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd
Summary
Dengue virus (DENV) consists of four serotypes that manifest similar symptoms, ranging from a mild febrile illness to a life-threatening dengue hemorrhagic fever [1]. As DENV is naturally transmitted to humans by mosquitoes, indicating the virus can infect and replicate in the mosquito cell during its journey from the midgut to salivary glands [6]. DENV has been detected in megakaryocyte progenitors and circulating platelets [10], suggesting that thrombocytopenia in dengue patients is closely associated with DENV infection [11, 12]. Such host cells are usually infected by DENV through receptor(s)-mediated endocytosis [13] and mostly end up undergoing apoptosis in response to dengue virus infection [14]. A huge number of viral particles from infected cells burst into the blood stream or a culture to become the source of infection for other cells
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