Arboviruses are an important group of pathogens that cause diseases of medical and veterinary concern worldwide1-14. Dengue, an important mosquito-borne virus transmitted mainly by Aedes aegypti, is a major public health issue in Latin America and the Caribbean.2-4 In Puerto Rico, the number of confirmed positive cases of Dengue in 2024 is 4,798.2 In Ecuador, 50,408 confirmed cases of Dengue were reported in 2024.3 The interactions of arboviruses with their host cells are complex, and frequently, the coexistence of two different viruses in the same cell results in the inhibition of replication in one of the viruses, which is a phenomenon called viral interference and can be exploited to develop antiviral strategies. The mechanisms responsible for viral interference have not been fully elucidated, but small RNAs could be involved.1,5-13
Persistent viral co-infections in arthropods have been studied by many researchers.1-14 Kanthong et al. (2008)7 produced stable, persistently infected C6/36 mosquito cell cultures by serial passage of exponentially growing whole cells infected with either a densovirus (AalDNV) or Dengue virus (DEN-2). Persistently infected cultures did not differ from naïve-cell cultures in growth rate and cell morphology. Immunocytochemistry revealed that 99-100% of the cells were coinfected and super-infection order had some effect on antigen distribution for the two viruses. Their results suggested that the capacity to support stable, viral co-infections may be a general phenomenon for arthropod cells, and such persistent infections would facilitate studies on interactions between co-infecting viruses. They also reported persistent, triple-virus co-infections in mosquito cells.
Anti-viral immunity in crustaceans and insects has been studied since 2004 at the laboratory of Dr. Tim Flegel in Thailand5-9 His group reported that mosquito cells accommodate balanced, persistent co-infections with a densovirus and Dengue. He later proposed the hypothesis for heritable, anti-viral immunity in crustaceans and insects. 9,10 In Penaeid shrimp, the densovirus Infectious Hypodermal and Hematopoietic Necrosis Virus (IHHNV) causes IHHN and runt deformity syndrome and mortalities in Penaeus stylirostris but not in P. vannamei. Co-infection of IHHNV with White Spot Syndrome Virus (WSSV) showed the typical clinical symptoms of WSSV infection, but co-infected shrimps did not have any other external deformities.11 Association of dual viral infection with mortality of P. vannamei farmed in India 12,13 and in Ecuador and Peru 14 have been reported. We present results of an in-depth review of scientific literature on molecular, genetic, and epigenetic mechanisms involved in densovirus-Dengue interactions in shrimp and address potential challenges for epidemiological control in the context of climate change and contamination by insecticides and pesticides used for combating pests and insects in crops of economic interest such as glyphosate-based herbicides.15
References
1 González-Flores, A. M., Salas-Benito M, Rosales-García, V. H., Zárate-Segura P. B., Del Ángel 5R. M., De Nova-Ocampo M. A., Salas-Benito, J. S. 2023. Characterization of Viral Interference in Aedes albopictus C6/36 Cells Persistently Infected with Dengue Virus 2. Pathogens. 12(9):1135. doi: 10.3390/pathogens12091135.
2 Torres, JR, González J. 2024. ProMED ESP http://www.isid.org. Noviembre 20, 2024.
3 Eventos Vectores, DNVE-SE1- SE35. 2024. Subsecretaria de Vigilancia, Prevención y Control de la Salud, Dirección Nacional de Vigilancia Epidemiológica, Enfermedades Transmitidas por Vectores. Ministerio de Salud Publica, Gobierno del Ecuador.
4 Torres JR, Orduna TA, Piña-Pozas M, Vázquez-Vega D, Sarti E. 2017. Epidemiological characteristics of Dengue disease in Latin America and in the Caribbean: A systematic review of the literature. Journal of Tropical Medicine Volume 2017, Article ID 8045435, 18 pages, https://doi.org/10.1155/2017/8045435.
5 Burivong P, Pattanakitsakul SN, Thongrungkiat S, Malasit P, Flegel TW. 2004. Markedly reduced severity of Dengue virus infection in mosquito cell cultures persistently infected with Aedes albopictus densovirus (AalDNV). Virology 329:261-269.
6 Flegel TW. 2007. Update on viral accommodation, a model for host-viral interaction in shrimp and other arthropods. Dev Comp Immunol 2007, 31:217-231.
7 Kanthong N, Khemnu N, Sriurairatana S, Pattanakitsakul S, Malasit P, Flegel TW. 2008. Mosquito cells accommodate balanced, persistent co-infections with a densovirus and Dengue virus. Dev Comp Immunol 32:1063-1075.
8 Kanthong N, Khemnu N, Pattanakitsakul S-N, Malasit P, Flegel TW. 2010. Persistent, triple-virus co-infections in mosquito cells. BMC Microbiology 10:14 http://www.biomedcentral.com/1471-2180/10/14
9 Flegel TW. 2009. Hypothesis for heritable, anti-viral immunity in crustaceans and insects. Biology Direct 2009, 4:32 doi:10.1186/1745-6150-4-32.
10 Flegel TW, Sritunyalucksana K. 2010. Shrimp molecular responses to viral pathogens. Marine Biotechnol 2010.
11 Du Y, Wang C, Y. Zhang. 2022. Viral Coinfections. Viruses 14(12):2645. doi: 10.3390/v14122645.
12 Otta, S.K.; Arulraj, R.; Ezhil Praveena, P.; Manivel, R.; Panigrahi, A.; Bhuvaneswari, T.; Ravichandran, P; Jithendran, K.P.; Ponniah, A.G. 2014. Association of dual viral infection with mortality of Pacific white shrimp (Litopenaeus vannamei) in culture ponds in India. VirusDisease 25, 63–68.
13 Saravanan K, Praveenraj J, Kiruba-Sankar R, Devi V, Biswas U, Kumar TS, Sudhagar A, El-Matbouli M, Kumar G. 2021. Co-Infection of Infectious Hypodermal and Hematopoietic Necrosis Virus (IHHNV) and White Spot Syndrome Virus (WSSV) in the Wild Crustaceans of Andaman and Nicobar Archipelago, India. Viruses. 13(7):1378. doi: 10.3390/v13071378.
14 Aranguren Caro LF, Gomez-Sanchez MM, Piedrahita Y, Mai HN, Cruz-Flores R, Alenton RRR, Dhar AK. 2022. Current status of infection with infectious hypodermal and hematopoietic necrosis virus (IHHNV) in the Peruvian and Ecuadorian shrimp industry. PLoS One. 2022 Aug 10;17(8):e0272456. doi: 10.1371/journal.pone.0272456. eCollection 2022.
15 LABIOFAM SA. Grupo Empresarial de Producciones Biofarmaceuticas y Quimicas, Boyeros, La Habana, Cuba (labiofam cu). BACTIVEC, Year 4, No. 1, 2014.