The Fight Against Zika: PI

Zika virus (ZIKV) is a new acute viral infectious disease mainly transmitted by Aedes mosquitoes. The clinical manifestations are usually mild, but some cases may develop serious symptoms such as neurological syndrome, birth defects, or stillbirth. The first reported case of human infection was in Uganda in 1964. Before 2007, it only caused a very small number of sporadic mild cases in some countries in Africa and Asia, so it did not attract attention. However, in the four months of 2007, it is estimated that 73% of the population over 3 years of age on Yap Island in Micronesia were infected with ZIKV. From October 2013 to April 2014, there were approximately 32,000 suspected cases of ZIKV infection in French Polynesia. From 2015 to 2016, the ZIKV epidemic began in Brazil, and then quickly spread to South and Central America. A total of 84 countries and regions around the world reported related epidemics. As of August 2017, in the Americas alone, nearly 790,000 suspicious and confirmed cases were reported throughout the epidemic, and 217,000 were confirmed. During this period, 3,490 patients with congenital syndrome related to ZIKV infection were reported, with 20 deaths reported.

It is currently believed that patients, recessively infected people, and infected animals are the main sources of infection. ZIKV is mainly transmitted by mosquitos such as Aedes aegypti and Aedes albopictus. Infectious urine may be another natural source of ZIKV, and mosquitoes may be infected by the virus when they reproduce in a contaminated aquatic environment. Other modes of transmission reported are infectious blood transfusion, sexual transmission, and vertical mother-to-child transmission. The basic reproduction number (R0) in Colombia at the beginning of the outbreak is estimated to be between 1.4 and 6.6, varying greatly from region to region. The R0 estimates for 13 countries/regions in the Americas and Rio de Janeiro are similar. The highest estimated R0 of the outbreak in the US in 2016 was 2.73.

ZIKV Structure

ZIKV is a single-stranded positive-stranded RNA virus belonging to the flavivirus genus of the Flaviviridae family (https://www.creative-biolabs.com/vaccine/vaccines-for-virus-from-flaviviridae-family.htm), which is divided into Asian virus strains and African virus strains. The family includes yellow fever virus (YFV), dengue virus (DENV), Japanese encephalitis virus (JEV), and West Nile virus (WNV), which spread by mosquito or tick bites, causing mild to serious life-threatening infections in humans. It was first isolated from monkey serum in the Zika Forest on the Victoria River in Uganda in 1947. The virus has a spherical shape with a diameter of about 40 to 70 nm and an envelope, whose genome is a single-stranded positive-stranded RNA with a length of about 10.8 kb. The ZIKV genome contains an open reading frame and non-coding regions at both ends, encoding a total of 3419 amino acids. From the 5'end to the 3'end, 3 structural proteins are encoded respectively, which are capsid protein (C), anterior membrane matrix protein/membrane matrix protein (prM/M), envelope protein (E), and 7 non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5).

The infection cycle of ZIKV is a relatively complicated process, similar to that of other flaviviruses. Viruses and host factors are utilized for the virus transcription, translation, immune evasion, and membrane structure reconstruction in cell membrane environment. First, the virus particles bind to host cell surface receptors and/or adsorption factors through the E protein, and then get internalized through clathrin-dependent endocytosis to form endocytic vesicles. The acidification of the vesicles causes the E protein conformation to change from a dimer to a hybrid trimer, which then fuses with the endocytic membrane and releases the viral genome into the host cytoplasm. Single-stranded positive RNA (ssRNA (+)) is translated into a polyprotein that is then cleaved into a variety of structural and non-structural proteins. Virus replication occurs on the surface of the endoplasmic reticulum (ER), and double-stranded RNA (dsRNA) is synthesized by viral RdRP. The dsRNA genome is transcribed and replicated to produce more viral mRNAs and single-stranded positive RNAs, which assemble into mature virus particles in the ER. After being transported by the Golgi apparatus, the prM protein is cleaved into M protein by furin, making it a fully mature and infectious virus particle. The newly formed virus particles are released into the extracellular environment and enter the next round of infection cycle.