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.