Whole genome sequencing of outbreak strains from 2017 to 2018 reveals an endemic clade of dengue 1 virus in Cameroon.

Dengue fever is expanding as a global public health threat including countries within Africa. For the past few decades, Cameroon has experienced sporadic cases of arboviral infections including dengue fever. Here, we conducted genomic analyses to investigate the origin and phylogenetic profile of Cameroon DENV-1 outbreak strains and predict the impact of emerging therapeutics on these strains. Bayesian and maximum-likelihood phylogenetic inference approaches were employed in virus evolutionary analyses. An in silico analysis was performed to assess the divergence in immunotherapeutic and vaccine targets in the new genomes. Six complete DENV-1 genomes were generated from 50 samples that met a clinical definition for DENV infection. Phylogenetic analyses revealed that the strains from the current study belong to a sub-lineage of DENV-1 genotype V and form a monophyletic taxon with a 2012 strain from Gabon. The most recent common ancestor (TMRCA) of the Cameroon and Gabon strains was estimated to have existed around 2008. Comparing our sequences to the vaccine strains, 19 and 15 amino acid (aa) substitutions were observed in the immuno-protective prM-E protein segments of the Dengvaxia® and TetraVax-DV-TV003 vaccines, respectively. Epitope mapping revealed mismatches in aa residues at positions E155 and E161 located in the epitope of the human anti-DENV-1 monoclonal antibody HMAb 1F4. The new DENV strains constitute a conserved genomic pool of viruses endemic to the Central African region that needs prospective monitoring to track local viral evolution. Further work is needed to ascertain the performance of emerging therapeutics in DENV strains from the African region.

Clustered rapid induction of apoptosis limits ZIKV and DENV-2 proliferation in the midguts of Aedes aegypti.

Inter-host transmission of pathogenic arboviruses such as dengue virus (DENV) and Zika virus (ZIKV) requires systemic infection of the mosquito vector. Successful systemic infection requires initial viral entry and proliferation in the midgut cells of the mosquito followed by dissemination to secondary tissues and eventual entry into salivary glands1. Lack of arbovirus proliferation in midgut cells has been observed in several Aedes aegypti strains2, but the midgut antiviral responses underlying this phenomenon are not yet fully understood. We report here that there is a rapid induction of apoptosis (RIA) in the Aedes aegypti midgut epithelium within 2 hours of infection with DENV-2 or ZIKV in both in vivo blood-feeding and ex vivo midgut infection models. Inhibition of RIA led to increased virus proliferation in the midgut, implicating RIA as an innate immune mechanism mediating midgut infection in this mosquito vector.

Chikungunya viruses containing the A226V mutation detected retrospectively in Cameroon form a new geographical subclade.

BACKGROUND: Chikungunya virus (CHIKV) is a re-emerging arbovirus associated with sporadic outbreaks in Cameroon since 2006. Viral whole genomes were generated to analyze the origins of evolutionary lineages, the potential of emergence/re-emergence, and to infer transmission dynamics of recent Cameroon CHIKV outbreak strains. METHODS: Samples collected between 2016 and 2019 during CHIKV outbreaks in Cameroon were screened for CHIKV using reverse transcription PCR (RT-PCR), followed by whole genome sequencing of positive samples. RESULTS: Three coding-complete CHIKV genomes were obtained from samples, which belong to an emerging sub-lineage of the East/Central/South African genotype and formed a monophyletic taxon with previous Central African strains. This clade, which we have named the new Central African clade, appears to be evolving at 3.0 × 10-4 nucleotide substitutions per site per year (95% highest posterior density (HPD) interval of 1.94 × 10-4 to 4.1 × 10-4). Notably, mutations in the envelope proteins (E1-A226V, E2-L210Q, and E2-I211T), which are known to enhance CHIKV adaptability and infectious potential in Aedes albopictus, were present in all strains and mapped to established high-density Ae. albopictus populations. CONCLUSIONS: These new CHIKV strains constitute a conserved genomic pool of an emerging sub-lineage, reflecting a putative vector host adaptation to Ae. albopictus, which has practically displaced Aedes aegypti from select regions of Cameroon.