Genotypic diversity and molecular characterization of DENV-2 in a Peruvian endemic region between 2016 and 2022: American/Asian genotype displacement

Yordi Tarazona-Castro ¹ Miguel Angel Aguilar-Luis ² Wilmer Silva-Caso ² Hugh Watson ^3* Victor Zavaleta-Gavidia ⁴ Ronald Aquino-Ortega ² Luis J. Del Valle ⁵ Jorge Bazan-Mayra ⁴ Egma Mayta Huatuco ¹ Juana del Valle-Mendoza ^2*

• ¹ National University of San Marcos, Lima, Lima, Peru
• ² Peruvian University of Applied Sciences, Lima, Peru
• ³ Evotec (France), Toulouse, France
• ⁴ Dirección Regional de Salud de Cajamarca, Cajamarca, Peru
• ⁵ Universitat Politecnica de Catalunya, Barcelona, Catalonia, Spain

Background: Dengue is the most prevalent acute febrile disease with serious clinical consequences in the Asian and American tropical and subtropical regions. It is a serious public health problem in Peru due to its hyperendemic nature as serotype 2 (DENV-2), aside from being the most prevalent serotype, causes the most serious clinical manifestations of the disease. This study focuses on the molecular characterization and intraserotypic diversity analysis of the DENV-2 that circulates in the endemic region of Cajamarca. Methods: Thirty-nine hundred sixty-seven (3,967) blood serum samples of patients with acute febrile illness (AFI) were analyzed between 2016 and 2022 to detect DENV and DENV-2 through real-time RT-PCR technique, and the viral envelope (E) gene was then sequenced by the Sanger method. Finally, the reconstruction of the phylogeny was performed using the maximum likelihood method.Results: Thirty-two (32) complete sequences of envelope gene were obtained in total, and the phylogenetic and characterization analysis of the amino acid sequence revealed that, during the 2016-2022 period, two DENV-2 genotypes, i.e., the Am/As genotype and the cosmopolitan genotype in their lineages 2 and C, respectively, circulated. Conclusion: Likewise, our findings showed that every studied outbreak was characterized by novel autochthonous variants in the case of the Am/As genotype and by an imported variant in the case of the cosmopolitan genotype; this, therefore, shows a temporal distribution of the intraserotypic variability that denotes the Am/As genotype displacement around 2021 and the rooting of the cosmopolitan genotype. The need of a constant genetic or genomic surveillance of the cosmopolitan virus arises in order to understand its distribution and diversification patterns in Peru.