New Advances on Zika Virus Research.

Zika virus (ZIKV) is an emerging mosquito-borne member of the Flaviviridae family that has historically been known to cause sporadic outbreaks, associated with a mild febrile illness, in Africa and Southeast Asia [...].

Zika virus (ZIKV) is an emerging mosquito-borne member of the Flaviviridae family that has historically been known to cause sporadic outbreaks, associated with a mild febrile illness, in Africa and Southeast Asia. However, the recent outbreaks of ZIKV in the Americas and its association with severe neurological disorders, including fetal microcephaly, Guillain-Barré syndrome, and ocular abnormalities, have caused a great social and sanitary alarm. The significance of ZIKV in human health, together with a lack of approved therapeutic (antivirals) or prophylactic (vaccines) interventions, has triggered a global effort to develop effective countermeasures against this pathogen, which has the potential to affect millions of people worldwide.

Since the re-emergence of the virus in 2015 in Brazil, massive advances have been made in practically all areas of the biology of ZIKV. In this Special Issue, we have assembled a collection of 32 research papers and reviews that cover recent advances on ZIKV research in molecular biology, replication and transmission, virus-host interactions, pathogenesis, epidemiology, vaccine development, antivirals, and diagnosis.

The first part of this Special Issue focuses on the development of ZIKV reverse genetic approaches, which constitute a powerful tool to answer important questions on the biology of ZIKV and for vaccine development. This theme is covered by a complete review of all ZIKV reverse genetic systems developed in the last years (Ávila-Pérez et al. [1]) and two research papers describing the generation of a ZIKV infectious clone by the mutational silencing of cryptical bacterial promoters present in the viral genome (Münster et al. [2]) and a Tet-inducible ZIKV infectious clone (Zhang et al. [3]).

The second topic of the Special Issue addresses recent advances in viral replication and transmission and is covered by three research articles (Barnard et al. [4]; Mlera and Bloom [5]; and Oliveira et al. [6]).

The third topic, virus-host interactions, includes two comprehensive reviews, one describing the molecular insights into ZIKV-host interactions (Lee et al. [7]) and other discussing the type I interferon (IFN) antagonist mechanisms used by flaviviruses, with a focus on the non-structural (NS)5 protein (Thurmond et al. [8]). In addition, this topic includes five research manuscripts that describe the impact of viral and host genetic variations on ZIKV infection (Yun et al. [9]), the effect of ZIKV infection on Heme Oxygenase expression (Kalamouni et al. [10]), the different effects of ZIKV infection in placenta and microglia cells (Martinez-Viedma and Pickett [11]), the effect of permethrin resistance on the vector transcriptome after ZIKV infection (Zhao et al. [12]), and the microRNA and mRNA profiling in infected neurons (Azouz et al. [13]).

The fourth subject area address new advances in ZIKV pathogenesis. This theme is covered by two reviews that describe ZIKV pathogenesis in the male reproductive tract (Stassen et al. [14]) and the ocular abnormalities induced by flavivirus infection (Singh et al. [15]), and five research articles that define fetal brain infection with ZIKV isolates not associated with microcephaly (Setoh et al. [16]), the pathogenesis of Asian and African ZIKV isolates in Indian Rhesus macaques (Rayner et al. [17]), the consequences of ZIKV infection in human pluripotent stem cell-derived neural progenitor cells and neurons (Goodfellow et al. [18]), the effect of a single mutation in the NS2A protein in virus pathogenesis (Márquez-Jurado et al. [19]), and the roles of the premembrane (prM) and envelop (E) proteins in ZIKV-mediated infection and neurocytotoxicity (Li et al. [20]).

The fifth section in the Special Issue covers the new advances in epidemiology and virus evolution, including a manuscript describing the evolutionary insight of ZIKV strains isolated in Latin America (Simón et al. [21]).

The next section focuses on ZIKV vaccines and antivirals, and contains three review documents (Garg et al. [22]; Alves et al. [23]; Saiz et al. [24]) and two research articles that describe the antiviral effect of silvestrol (Elgner et al. [25]) and oxysterol 7-ketocholesterol (Willard et al. [26]) in ZIKV replication.

The last section in this Special Issue covers new advances in the molecular diagnostic of ZIKV, and includes a comprehensive review (Mantke et al. [27]) and five research articles that describe the development and characterization of several ZIKV diagnostic methods (Bhadra et al. [28]; de Ory et al. [29]; Zhang et al. [30]; Taylor et al. [31]; Amaro et al. [32]).

We would like to thank all contributing authors for their participation, effort and hard work in putting together this Special Issue. We would also like to thank the Editorial Office at Viruses for all the help, support, and advice with this Special Issue. We hope this Special Issue offers a comprehensive view of the recent advances in ZIKV research and stimulates research for future studies aimed at understanding ZIKV evolution, virus-host-interaction, pathogenesis, and the development of effective countermeasures to combat ZIKV infection.