Overview of Zika virus (ZIKV) infection in regards to the Brazilian epidemic

Brazilian Journal of Medical and Biological Research (2016) 49(5): e5420, http://dx.doi.org/10.1590/1414-431X20165420 ISSN 1414-431X Overview 1/11 Overview of Zika virus (ZIKV) infection in regards to the Brazilian epidemic S.N. Slavov1,2, K.K. Otaguiri1,3, S. Kashima1,3 and D.T. Covas1,2 1 Hemocentro de Ribeirão Preto, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil 2 Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil 3 Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, Ribeirão Preto, SP, Brasil Abstract Zika virus (ZIKV), a mosquito-borne flavivirus, belongs to the Flaviviridae family, genus Flavivirus. ZIKV was initially isolated in 1947 from a sentinel monkey in the Zika forest, Uganda. Little clinical importance was attributed to ZIKV, once only few symptomatic cases were reported in some African and Southeast Asiatic countries. This situation changed in 2007, when a large outbreak was registered on the Yap Island, Micronesia, caused by the Asian ZIKV lineage. Between 2013 and 2014, ZIKV spread explosively and caused many outbreaks in different islands of the Southern Pacific Ocean and in 2015 autochthonous transmission was reported in Brazil. Currently, Brazil is the country with the highest number of ZIKV-positive cases in Latin America. Moreover, for the first time after the discovery of ZIKV, the Brazilian scientists are studying the possibility for the virus to cause severe congenital infection related to microcephaly and serious birth defects due to the time-spatial coincidence of the alarming increase of newborns with microcephaly and the Brazilian ZIKV epidemic. The present review summarizes recent information for ZIKV epidemiology, clinical picture, transmission, diagnosis and the consequences of this emerging virus in Brazil. Key words: Zika virus; ZIKV; Transmission; Epidemiology; Congenital infection; Brazil Introduction Zika virus (ZIKV) was isolated in 1947 from a febrile sentinel Rhesus monkey from the Zika forest on the banks of lake Victoria, Uganda (1). The virus was not linked to a human infection until 1954, when ZIKV was detected in three patients during an outbreak of jaundice in East Nigeria (2). Almost at the same time, ZIKV has been isolated from Aedes (Stegomya) africanus mosquitoes, in Africa, and Aedes aegypti, in Southeast Asia (3,4). From 1954 to 1993 serologic evidence for ZIKV infection had been reported from various African countries including Kenya (5), Sierra Leone (6), Gabon (7,8), Ivory Coast (9), Central African Republic (10), and Senegal (11). By this time, in Asia, ZIKV has been detected in individuals with acute fever from Central Java and Lombok Island, Indonesia (12,13). This early serological evidence demonstrated that ZIKV circulates in some countries of SubSaharan Africa and Southeast Asia with relatively low number of symptomatic cases (o10 official cases). The situation changed in 2007, when an outbreak of a Dengue virus (DENV)-like disease characterized by rash, conjunctivitis and arthralgia was registered on the Yap Island, Micronesia (Figure 1). Rapid DENV tests suggested that it was the etiological agent for that outbreak and the collected samples were sent to the Centers for Disease Control and Prevention (CDC) Arbovirus Diagnostic Laboratory for viral confirmation. The performed tests with Flaviviridae genus consensus primers demonstrated sequences sharing 90% nucleotide identity with ZIKV. Therefore, the Yap Island epidemic was caused by ZIKV and not DENV and, specifically, by the ZIKV Asian lineage (14). The Yap Island outbreak demonstrated that ZIKV was not restricted to Africa and Southeast Asia and could cause epidemics outside its habitual occurrence. Nevertheless, Micronesia is geographically close to the countries of Southeast Asia, where ZIKV is endemic and it could be supposed that travelers or trade have introduced the virus in Oceania. Surprisingly, between 2013 and 2014, ZIKV continued its spread through the Southern Pacific and caused its largest outbreak in French Polynesia with an estimated occurrence of 19,000 cases in various islands from this region. The identified genotype, similarly to the epidemic in the Yap Island, Correspondence: S.N. Slavov: <> Received March 21, 2016 | Accepted April 1, 2016 Braz J Med Biol Res | doi: 10.1590/1414-431X20165420 Overview of Zika virus (ZIKV) belonged to the Asiatic lineage and its global expansion was suspected (15). Moreover, the Asian lineage expanded rapidly to many South Pacific islands and outbreaks were reported from New Caledonia, the Cook Islands and the Easter Island, Chile (16) (Figure 1). The first official report for ZIKV autochthonous transmission in Brazil was documented in March 2015 in the city of Natal, in the Northeast part of the country. The patients presented with a benign disease characterized by mild fever, macopapular rash, headache, conjunctivitis, arthralgia and edema, similar to the symptoms caused by DENV, however all were DENV-negative (17). After confirmation of autochthonous transmission of ZIKV in Brazil, it was speculated that ZIKV entered the country during the 2014 World Football Championship; however, no countries endemic for ZIKV infection were competing in this event. The most probable ZIKV introduction in Brazil seems to have occurred during the Va’a World Sprint Championship, where competitors from countries with ZIKV outbreaks, i.e., French Polynesia, New Caledonia, Cook Islands, and Easter Island, have been participating (18). This event coincided with the first report of autochthonous transmission of ZIKV in Brazil and with the confirmation of the Asiatic lineage of the circulating strain. Currently, Brazil is the country with the highest number of ZIKV-positive cases in Latin America with circulation of the virus in almost the entire national territory. Viral characteristics ZIKV belongs to the Flaviviridae family, genus Flavivirus, closely related to the Spondweni virus (19). Therefore, ZIKV has the typical flavivirus organization of the virion with an icosahedral, enveloped particle. The genome is a singlestranded, positive-sense RNA of approximately 11 kb. The genomic organization follows that of the flaviviruses with two flanking non-coding regions (NCR), i.e. 59 and 39, and a long open reading frame encoding a single polyprotein: (NCR59)-C-prM-E-NS1-NS2A-NS2BNS3-NS4A-NS4BNS5-(NCR39). The polyprotein is cleaved into capsid (C), precursor of membrane (prM), envelope (E) and seven nonstructural proteins (NS) (20). The E protein, a major viral envelope protein, is involved in receptor binding and membrane fusion. The domain III of the E protein contains different antigenic epitopes that may be important targets for serological assays, neutralizing antibodies, and vaccines (21). Worldwide dissemination of ZIKV is th (...truncated)