Dengue Virus Infection of Aedes aegypti Requires a Putative Cysteine Rich Venom Protein

Londoño-Rentería, Berlin; Troupin, Andrea; Conway, Michael J.; Vesely, Diana; Ledizet, Michael; Roundy, Christopher M.; Cloherty, Erin; Jameson, Samuel; Vanlandingham, Dana L.; Higgs, Stephen; Fikrig, Erol; Colpitts, Tonya M.

doi:10.1371/journal.ppat.1005202

Cited by 52 publications

(56 citation statements)

References 78 publications

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“…Mosquito proteins related to virus infection were selected as immunogens and showed a role in blocking dengue virus infection. One of the immunogens is the mosquito C-type lectin protein (69)(70)(71). Although several trials were studied, research into TBVs that block infection needs more work in the future (70).…”

Section: Fig 6 Anti-mosgctl-7 Serum Inhibits Jev Infection In Vivo Anmentioning

confidence: 99%

mosGCTL-7, a C-Type Lectin Protein, Mediates Japanese Encephalitis Virus Infection in Mosquitoes

Liu

Qian

Jung

et al. 2017

J Virol

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Japanese encephalitis virus (JEV) is an arthropod-borne flavivirus prevalent in Asia and the Western Pacific and is the leading cause of viral encephalitis. JEV is maintained in a transmission cycle between mosquitoes and vertebrate hosts, but the molecular mechanisms by which the mosquito vector participates in transmission are unclear. We investigated the expression of all C-type lectins during JEV infection in Aedes aegypti. The C-type lectin mosquito galactose-specific C-type lectin 7 (mosGCTL-7) (VectorBase accession no. AAEL002524) was significantly upregulated by JEV infection and facilitated infection in vivo and in vitro. mosGCTL-7 bound to the N-glycan at N154 on the JEV envelope protein. This recognition of viral N-glycan by mosGCTL-7 is required for JEV infection, and we found that this interaction was Ca 2ϩ dependent. After mosGCTL-7 bound to the glycan, mosPTP-1 bound to mosGCTL-7, promoting JEV entry. The viral burden in vivo and in vitro was significantly decreased by mosPTP-1 double-stranded RNA (dsRNA) treatment, and infection was abolished by anti-mosGCTL-7 antibodies. Our results indicate that the mosGCTL-7/mosPTP-1 pathway plays a key role in JEV infection in mosquitoes. An improved understanding of the mechanisms underlying flavivirus infection in mosquitoes will provide further opportunities for developing new strategies to control viral dissemination in nature.IMPORTANCE Japanese encephalitis virus is a mosquito-borne flavivirus and is the primary cause of viral encephalitis in the Asia-Pacific region. Twenty-four countries in the WHO Southeast Asia and Western Pacific regions have endemic JEV transmission, which exposes Ͼ3 billion people to the risks of infection, although JEV primarily affects children. C-type lectins are host factors that play a role in flavivirus infection in humans, swine, and other mammals. In this study, we investigated C-type lectin functions in JEV-infected Aedes aegypti and Culex pipiens pallens mosquitoes and cultured cells. JEV infection changed the expression of almost all C-type lectins in vivo and in vitro, and mosGCTL-7 bound to the JEV envelope protein via an N-glycan at N154. Cell surface mosPTP-1 interacted with the mosGCTL-7-JEV complex to facilitate virus infection in vivo and in vitro. Our findings provide further opportunities for developing new strategies to control arbovirus dissemination in nature.

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Section: Fig 6 Anti-mosgctl-7 Serum Inhibits Jev Infection In Vivo Anmentioning

confidence: 99%

mosGCTL-7, a C-Type Lectin Protein, Mediates Japanese Encephalitis Virus Infection in Mosquitoes

Liu

Qian

Jung

et al. 2017

J Virol

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“…Blocking the CRVP379 protein with either RNAi or specific antisera inhibited the DENV infection in A. aegypti , representing a broad preventive and therapeutic measure for dengue control. 79 Taken together, immunization with DENV-related mosquito susceptibility factors may also be a feasible transmission-blocking vaccine approach for dengue prevention.…”

Section: Novel Immunization Strategies For Dengue Preventionmentioning

confidence: 99%

Vaccines and immunization strategies for dengue prevention

Liu

Cheng

2016

Emerging Microbes & Infections

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Dengue is currently the most significant arboviral disease afflicting tropical and sub-tropical countries worldwide. Dengue vaccines, such as the multivalent attenuated, chimeric, DNA and inactivated vaccines, have been developed to prevent dengue infection in humans, and they function predominantly by stimulating immune responses against the dengue virus (DENV) envelope (E) and nonstructural-1 proteins (NS1). Of these vaccines, a live attenuated chimeric tetravalent DENV vaccine developed by Sanofi Pasteur has been licensed in several countries. However, this vaccine renders only partial protection against the DENV2 infection and is associated with an unexplained increased incidence of hospitalization for severe dengue disease among children younger than nine years old. In addition to the virus-based vaccines, several mosquito-based dengue immunization strategies have been developed to interrupt the vector competence and effectively reduce the number of infected mosquito vectors, thus controlling the transmission of DENV in nature. Here we summarize the recent progress in the development of dengue vaccines and novel immunization strategies and propose some prospective vaccine strategies for disease prevention in the future.

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“…Development of vaccines is hampered by the large number of emerging flaviviruses around the globe and antibody-dependent enhancement (Guzman et al, 2013;Aguiar & Halstead, 2016;Dejnirattisai et al, 2016). It is theoretically possible to target vector proteins or cellular pathways as a method to prevent flavivirus transmission (Cheng et al, 2010;Conway et al, 2013Conway et al, , 2014Conway et al, , 2016Londono-Renteria et al, 2015;Troupin et al, 2016). Fundamental to the success of a vectorbased strategy is the reliance on a protein or cellular pathway for infection.…”

Section: Introductionmentioning

confidence: 99%

“…Infected blood from a vertebrate host is stored in the midgut. Infection of midgut epithelial cells requires bypassing the peritrophic matrix and forming specific interactions with secreted and membrane-bound receptors (Kato et al, 2008;Cheng et al, 2010;Londono-Renteria et al, 2015). The few virions that survive the midgut and establish an infection represent a genetic bottleneck (Coffey et al, 2008;Forrester et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

“…Acquisition-blocking vaccines (ABVs) are currently being developed to prevent Plasmodium infection in their Anopheles transmission vector (Farrance et al, 2011;Miyata et al, 2011;Mathias et al, 2012). ABV candidates have also been identified that reduce mosquito midgut infection with DENV and West Nile virus (Cheng et al, 2010;Londono-Renteria et al, 2015). These data suggest that it is theoretically possible to interrupt disease transmission by targeting vector proteins or cellular pathways.…”

Section: Introductionmentioning

confidence: 99%

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Low density lipopolyprotein inhibits flavivirus acquisition in Aedes aegypti

Wagar

Tree

Mpoy

et al. 2017

Insect Molecular Biology

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Aedes aegypti is the primary vector of a number of human pathogens including dengue virus (DENV) and Zika virus (ZIKV). Ae. aegypti acquires these viruses during the processing of bloodmeals obtained from an infected vertebrate host. Vertebrate blood contains a number of factors that have the potential to modify virus acquisition in the mosquito. Interestingly, low density lipopolyprotein (LDL) levels are decreased during severe DENV infection. Accordingly, we hypothesized that LDL is a modifiable factor that can influence flavivirus acquisition in the mosquito. We found that LDL is endocytosed by Ae. aegypti cells in a dynamin-dependent manner. LDL is also endocytosed by midgut epithelial cells and accumulates at the luminal midgut epithelium during bloodmeal digestion. Importantly, pretreatment with LDL, but not high density lipopolyprotein (HDL), significantly inhibited both DENV and ZIKV infection in vitro, and LDL inhibited ZIKV infection in vivo. This study identifies human LDL or 'bad cholesterol' as a modifiable factor that can inhibit flavivirus acquisition in Ae. aegypti. Identification of modifiable blood factors and critical cellular interactions that mediate pathogen acquisition may lead to novel strategies to disrupt the transmission cycle of vector-borne diseases.

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Dengue Virus Infection of Aedes aegypti Requires a Putative Cysteine Rich Venom Protein

Cited by 52 publications

References 78 publications

mosGCTL-7, a C-Type Lectin Protein, Mediates Japanese Encephalitis Virus Infection in Mosquitoes

mosGCTL-7, a C-Type Lectin Protein, Mediates Japanese Encephalitis Virus Infection in Mosquitoes

Vaccines and immunization strategies for dengue prevention

Low density lipopolyprotein inhibits flavivirus acquisition in Aedes aegypti

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