- Volume 104, Issue 3, 2023

Dengue virus (DENV) is the mosquito-borne virus of greatest human health concern. There are four serotypes of DENV (1-4) that co-circulate in endemic areas. Each serotype of DENV is individually capable of causing the full spectrum of disease, ranging from self-resolving dengue fever to the more severe dengue haemorrhagic fever (DHF) or dengue shock syndrome (DSS). Based on data published by the CDC, one in four people who become infected with dengue will become ill. Of those that do develop symptomology, the symptoms can range from mild to severe. Symptoms can vary from rash, ocular aches and pains to more intense symptoms in the manifestation of severe dengue. Roughly, 1 in 20 people who become ill will develop severe dengue, which can result in shock, internal bleeding and death. There is currently no specific treatment for dengue and only one licensed vaccine (Dengvaxia) for children 9 through 16 years of age in just a few countries. Despite its licensure for clinical use, Dengvaxia has performed with low efficacy in children and dengue naïve individuals and critically has resulted in increased risk of developing severe dengue in young, vaccinated recipients. Currently, there are various novel strategies for the development of a dengue vaccine. In this review we have conducted a detailed overview of the DENV vaccine landscape, focusing on nine vaccines in the pipeline to provide a comprehensive overview of the most state-of-the-art developments in strategies for vaccines against DENV.

Members of the family Sphaerolipoviridae have non-enveloped tailless icosahedral virions with a protein-rich internal lipid membrane. The genome is a linear double-stranded DNA of about 30 kbp with inverted terminal repeats and terminal proteins. The capsid has a pseudo triangulation T=28 dextro symmetry and is built of two major capsid protein types. Spike complexes decorate fivefold vertices. Sphaerolipoviruses have a narrow host range and a lytic life cycle, infecting haloarchaea in the class Halobacteria (phylum Euryarchaeota). This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Sphaerolipoviridae, which is available at ictv.global/report/sphaerolipoviridae.

Seneca Valley virus (SVV, also known as Senecavirus A), an oncolytic virus, is a nonenveloped, positive-strand RNA virus and the sole member of the genus Senecavirus within the family Picornaviridae. The mechanisms of SVV entry into cells are currently almost unknown. In the present study, we found that SVV entry into HEK293T cells is acidic pH-dependent by using ammonium chloride (NH4Cl) and chloroquine, both of which could inhibit SVV infection. We confirmed that dynamin II is required for SVV entry by using dynasore, silencing the dynamin II protein, or expressing the dominant-negative (DN) K44A mutant of dynamin II. Then, we discovered that chlorpromazine (CPZ) treatment or knockdown of the clathrin heavy chain (CLTC) protein significantly inhibited SVV infection. In addition, overexpression of CLTC promoted SVV infection. Caveolin-1 and membrane cholesterol were also required for SVV endocytosis. Notably, utilizing genistein, EIPA or nocodazole, we observed that macropinocytosis and microtubules are not involved in SVV entry. Furthermore, overexpression of the Rab7 and Rab9 proteins but not the Rab5 or Rab11 proteins promoted SVV infection. The findings were further validated by the knockdown of four Rabs and Lamp1 proteins, indicating that after internalization, SVV is transported from late endosomes to the trans-Golgi network (TGN) or lysosomes, respectively, eventually releasing its RNA into the cytosol from the lysosomes. Our findings concretely revealed SVV endocytosis mechanisms in HEK293T cells and provided an insightful theoretical foundation for further research into SVV oncolytic mechanisms.