Zika virus

From Wikipedia, the free encyclopedia

This article is about the virus. For the disease, see Zika fever. For the current
outbreak, see Zika virus outbreak (2015present).
Zika virus

Electron micrograph of the Zika virus.

Virus particles are 40 nm in diameter,
with an outer envelope and a dense
inner core.[1]

Virus classification
Group:

Group IV ((+)ssRNA)

Family:

Flaviviridae

Genus:

Flavivirus

Species:

Zika virus

Zika virus /zik, zk/[2][3][4][5] (ZIKV) is a member of

the virus family Flaviviridae and the genus Flavivirus.[6] It is spread by daytimeactive Aedes mosquitoes, such as A. aegypti and A. albopictus.[6] Its name comes
from the Zika Forest of Uganda, where the virus was first isolated in 1947.[7] Zika

virus is related to dengue, yellow fever, Japanese encephalitis, and West

Nile viruses.[7]
The infection, known as Zika fever, often causes no or only mild symptoms,
similar to a mild form of dengue fever.[6] It is treated by rest.[8]Since the 1950s, it
has been known to occur within a narrow equatorial belt from Africa to Asia. The
virus spread eastward across thePacific Ocean between 2013 and 2014 to
French Polynesia, New Caledonia, the Cook Islands, and Easter Island, and in
2015 to Mexico,Central America, the Caribbean, and South America, where
the Zika outbreak has reached pandemic levels.[9] As of 2016, the illness cannot
be prevented by medications or vaccines.[8] Zika fever in pregnant women is
associated with microcephaly but it is unclear whether the virus is the cause.[6]
[10]
An association with the neurologic conditions, GuillainBarr syndrome, has
been found in adults.[6]
In January 2016, the U.S. Centers for Disease Control and Prevention (CDC)
issued travel guidance on affected countries, including the use of enhanced
precautions, and guidelines for pregnant women including considering
postponing travel.[11][12] Other governments or health agencies also issued similar
travel warnings,[13][14][15] while Colombia, the Dominican Republic, Ecuador, El
Salvador, and Jamaica advised women to postpone getting pregnant until more
is known about the risks.[14][16]
Contents
[hide]

1Virology
2Transmission
o 2.1Mosquito
o 2.2Sexual
o 2.3During pregnancy
o 2.4Other, unproven
3Pathogenesis
4Zika fever
5Vaccine development

 6History
o 6.1Virus isolation in monkeys and mosquitoes, 1947
o 6.2First evidence of human infection, 1952
o 6.3Spread in equatorial Africa and to Asia, 19511981
o 6.4Micronesia, 2007
o 6.5Oceania, 20132014
o 6.6Americas, 2015present
7References
8External links

Virology

A video explanation of Zika virus and Zika fever

The Zika virus belongs to Flaviviridae and the genus Flavivirus, and is thus
related to the dengue, yellow fever, Japanese encephalitis, and West
Nile viruses. Like other flaviviruses, Zika virus is enveloped and icosahedral and
has a nonsegmented, single-stranded, positive-sense RNA genome. It is most
closely related to the Spondweni virus and is one of the two viruses in the
Spondweni virus clade.[17][18]
A positive-sense RNA genome can be directly translated into viral proteins. In
other flaviviruses, such as the similarly sized West Nile virus, the RNA genome
genes encode seven nonstructural proteins and three structural proteins. The
structural proteins encapsulate the virus. The replicated RNA strand is held within
a nucleocapsid formed from 12-kDa protein blocks; the capsid is contained within
a host-derived membrane modified with two viral glycoproteins. Replication of the
viral genome would first require creation of an anti-sense nucleotide strand.[citation
needed]

There are two lineages of the Zika virus: the African lineage, and the Asian
lineage.[19] Phylogenetic studies indicate that the virus spreading in the Americas
is most closely related to the Asian strain, which circulated in French Polynesia
during the 20132014 outbreak.[19][20] The complete genome sequence of the Zika
virus has been published.[21] Western Hemisphere Zika virus is found to be 89%
identical to African genotypes, but is most closely related to the strain found in
French Polynesia during 20132014.[22]

Transmission
The vertebrate hosts of the virus were primarily monkeys in a socalled enzootic mosquito-monkey-mosquito cycle, with only occasional
transmission to humans. Before the current pandemic began in 2007, Zika virus
"rarely caused recognized 'spillover' infections in humans, even in highly enzootic
areas". Infrequently, other arboviruses have become established as a human
disease though, and spread in a mosquitohumanmosquito cycle, like the
yellow fever virus and the dengue fever virus (both flaviruses), and
the chikungunya virus (a togavirus).[23]

Mosquito

Global Aedes aegypti predicted distribution. The map depicts the probability of occurrence
(blue=none, red=highest occurrence).

The Zika virus is spread by daytime-active mosquitoes. It is primarily spread by

the female Aedes aegypti in order to lay eggs,[24]:2 but has been isolated from a
number of arboreal mosquito species in the Aedes genus, such as A.
africanus, A. apicoargenteus, A. furcifer, A. hensilli, A. luteocephalus and A.
vittatus with an extrinsic incubation period in mosquitoes of about 10 days.[25]
The true extent of the vectors is still unknown. The Zika virus has been detected
in many more species of Aedes, along withAnopheles coustani, Mansonia
uniformis, and Culex perfuscus, although this alone does not incriminate them as
a vector.[26]
Transmission by A. albopictus, the tiger mosquito, was reported from a 2007
urban outbreak in Gabon where it had newly invaded the country and become
the primary vector for the concomitant chikungunya and dengue virus outbreaks.
[27]
There is concern for autochthonous infections in urban areas of European

countries infested by A. albopictus because the first two cases of laboratory

confirmed Zika virus infections imported into Italy were reported from viremic
travelers returning from French Polynesia.[28]
The potential societal risk of Zika virus can be delimited by the distribution of the
mosquito species that transmit it. The global distribution of the most cited carrier
of Zika virus, A. aegypti, is expanding due to global trade and travel.[29] A.
aegypti distribution is now the most extensive ever recorded across all
continents including North America and even the European periphery (Madeira,
the Netherlands, and the northeastern Black Sea coast).[30] A mosquito population
capable of carrying the Zika virus has been found in aCapitol Hill neighborhood
of Washington, D. C., and genetic evidence suggests they survived at least four
consecutive winters in the region. The study authors conclude that mosquitos are
adapting for persistence in a northern climate.[31]
Since 2015, news reports have drawn attention to the spread of Zika in Latin
America and the Caribbean.[32] The countries and territories that have been
identified by the Pan American Health Organisation as having experienced "local
Zika virus transmission" are Barbados, Bolivia, Brazil, Colombia, the Dominican
Republic, Ecuador, El Salvador, French Guiana, Guadeloupe, Guatemala,
Guyana, Haiti, Honduras, Martinique, Mexico, Panama, Paraguay, Puerto Rico,
Saint Martin, Suriname, and Venezuela.[33][34][35]

Sexual
As of February 2016, there are three reported cases indicating that Zika virus
could possibly be sexually transmitted.[36] In 2014, Zika virus capable of growth in
lab culture was found in the semen of a man at least two weeks (and possibly up
to 10 weeks) after he fell ill with Zika fever.[36][37] The second report is of a United
States biologist who had been bitten many times while studying mosquitoes in
Senegal. Six days after returning home in August 2008, he fell ill with symptoms
of Zika fever but not before having unprotected intercourse with his wife, who had
not been outside the US in 2008. She subsequently developed symptoms of Zika
fever, and Zika antibodies in both the biologist's and his wife's blood confirmed
the diagnosis.[36][38] In the third case, in early February 2016 the Dallas
County Health and Human Services department reported that a person
contracted Zika fever after sexual contact with an ill person who had recently
returned from a high risk country. This case is still under investigation.[36]
[39]
Fourteen additional cases of possible sexual transmission are under
investigation. All cases involve transmitting the Zika virus from men to women
and it is unknown whether women can transmit Zika virus to their sexual
partners.[40]
As of February 2016, the CDC recommends that men "who reside in or have
traveled to an area of active Zika virus transmission who have a pregnant partner
should abstain from sexual activity or consistently and correctly use condoms

during sex (i.e., vaginal intercourse, anal intercourse, or fellatio) for the duration
of the pregnancy." Men who reside in or have traveled to an area of active Zika
virus transmission and their non-pregnant sex partners "might consider"
abstinence or condom use. The CDC did not specify how long these practices
should be followed with non-pregnant partners because the "incidence and
duration of shedding in the male genitourinary tract is limited to one case report"
and that "testing of men for the purpose of assessing risk for sexual transmission
is not recommended."[36]

During pregnancy
In 2015, Zika virus RNA was detected in the amniotic fluid of two pregnant
women whose fetuses had microcephaly, indicating that the virus had crossed
the placenta and could have caused a mother-to-child infection.[41] Up until
February 2016 the link was thought possible but unproven.[42][43][44] Brain tissue
from two newborns with microcephaly who died within 20 hours of birth and
placenta and other tissue of two miscarriages (11 and 13 weeks) from Rio
Grande do Norte in Brazil tested positive for Zika virus by RT-PCR at the CDC.
[45]
In a cohort study of pregnant women in Rio de Janeiro, Zika virus infection was
associated with fetal death, placental insufficiency, fetal growth restriction, and
central nervous system (CNS) injury (microcephaly and/or ventricular
calcifications or other lesions) in 12 of 42 fetuses studied using ultrasound.[46]
According to the WHO on 5 February 2016, a causal link between the Zika virus
and microcephaly was "strongly suspected but not yet scientifically proven" and
"Although the microcephaly cases in Brazil are spatio-temporally associated with
the Zika outbreak, more robust investigations and research is needed to better
understand this potential link."[47]
On 5 February 2016, the United States CDC updated its health care provider
guidelines for pregnant women and women of reproductive age. The new
recommendations include offering serologic testing to pregnant women without
Zika fever symptoms who have returned from areas with ongoing Zika virus
transmission in the last 212 weeks; and for pregnant women without Zika
symptoms living in such areas, they recommend testing at the beginning of
prenatal care and follow-up testing in the fifth month of pregnancy.[48]

Other, unproven
As of February 2016 there are no confirmed cases of Zika virus transmission
through blood transfusions.[49] A potential risk is supected based on a study
conducted between November 2013 and February 2014 during the Zika outbreak
in French Polynesia, in which 2.8% (42) of blood donors tested positive for the
Zika virus RNA and were asymptomatic at the time of blood donation. Eleven of
those positive donors reported symptoms of Zika fever after their donation, and
only three of 34 samples grew in culture.[50]Since January 2014 nucleic acid

testing of blood donors was implemented in French Polynesia to prevent

unintended transmission.[50]

Pathogenesis
Zika virus replicates in the mosquito's midgut epithelial cells and then its salivary
gland cells. After 510 days, ZIKV can be found in the mosquitos saliva which
can then infect human. If the mosquitos saliva is inoculated into human skin, the
virus infect epidermal keratinocytes, skin fibroblasts in the skin and the
Langerhans cells. The pathogenesis of the virus is hypothesized to continue with
a spread to lymph nodes and the bloodstream.,[17][51] Flaviviruses generally
replicate in the cytoplasm, but Zika virus antigens have been found in infected
cell nuclei.[52]

Zika fever
Main article: Zika fever

Rash on an arm due to Zika virus

Common symptoms of infection with the virus include mild

headaches, maculopapular rash, fever, malaise, conjunctivitis, and joint pains.
Three well-documented cases of Zika virus were described in brief in 1954,
whereas a detailed description was published 1964; it began with a mild
headache, and progressed to a maculopapular rash, fever, and back pain. Within
two days, the rash started fading, and within three days, the fever resolved and
only the rash remained. Thus far, Zika fever has been a relatively mild disease of
limited scope, with only one in five persons developing symptoms, with no
fatalities, but its true potential as a viral agent of disease is unknown.[25]
As of 2016, no vaccine or preventative drug is available. Symptoms can be
treated with rest, fluids, and paracetamol (acetaminophen), whileaspirin and
other nonsteroidal anti-inflammatory drugs should be used only when dengue
has been ruled out to reduce the risk of bleeding.[53]

There is a link between Zika fever and neurologic conditions in infected adults,
including cases of the GuillainBarr syndrome.[23]

Vaccine development
Effective vaccines exist for several flaviviruses. Vaccines for yellow fever
virus, Japanese encephalitis, and tick-borne encephalitis were introduced in the
1930s, while the vaccine for dengue fever only became available for use in the
mid-2010s.[54][55][56] Early in March 2016, 18 companies and institutions
internationally were developing vaccines against Zika virus, but none had yet
reached clinical trials.[57] WHO experts have suggested that the priority should be
to develop inactivated and other non-live vaccines that have a safety profile
suitable for use in pregnant women and those of childbearing age.[57]
Work has begun in the USA towards developing a vaccine for the Zika virus.
[58]
The researchers at the Vaccine Research Center have extensive experience
from working with vaccines for other viruses such as West Nile virus,
chikungunya virus, and dengue fever.[58] Nikos Vasilakis of the Center for
Biodefense and Emerging Infectious Diseasespredicted that it may take two
years to develop a vaccine, but 10 to 12 years may be needed before an
effective Zika virus vaccine is approved by regulators for public use.[59]
An Indian company, Bharat Biotech International, reported in early February 2016
that it was working on vaccines for the Zika virus.[60] The company is working on
two approaches to a vaccine: "recombinant", involving genetic engineering, and
"inactivated", where the virus is incapable of reproducing itself but can still trigger
an immune response. The company announced animal trials of the inactivated
version would commence in late February.[61]

History
See also: Zika fever Epidemiology

Countries that have past or current evidence of Zika virus transmission (as of January 2016)
[62]

Spread of the Zika virus[63][64][65]

Virus isolation in monkeys and mosquitoes, 1947

The virus was first isolated in April 1947 from a rhesus macaque monkey that
had been placed in a cage in the Zika Forest of Uganda, near Lake Victoria, by
the scientists of the Yellow Fever Research Institute.[66] A second isolation from
the mosquito A. africanus followed at the same site in January 1948.[67] When the
monkey developed a fever, researchers isolated from its serum a "filterable
transmissible agent" that was named Zika virus in 1948.[25][68]

First evidence of human infection, 1952

Zika virus had been known to infect humans from the results of serological
surveys in Uganda and Nigeria. A serosurvey of 84 people of all ages showed 50
had antibodies, with all above 40 years of age being immune.[69]
It was not until 1954 that the successful isolation of Zika virus from a human was
published. This came as part of a 1952 outbreak investigation of jaundice
suspected to be yellow fever. It was found in the blood of a 10 year old Nigerian
female with low grade fever, headache, and evidence of malaria, but no jaundice,
who recovered within three days. Blood was injected into the brain of laboratory
mice, followed by up to 15 mice passages. The virus from mouse brains was
then tested in neutralization tests using rhesus monkey sera specifically immune
to Zika virus. In contrast, no virus was isolated from the blood of two infected
adults with fever, jaundice, cough, diffuse joint pains in one and fever, headache,
pain behind the eyes and in the joints. Infection was proven by a rise in Zika virus
specific serum antibodies.[69] A 1952 research study conducted in India had
shown a "significant number" of Indians tested for Zika had exhibited an immune
response to the virus, suggesting it had long been widespread within human
populations.[70]

Spread in equatorial Africa and to Asia, 19511981

From 1951 through 1981, evidence of human infection with Zika virus was
reported from other African countries, such as the Central African Republic,
Egypt, Gabon, Sierra Leone, Tanzania, and Uganda, as well as in parts of Asia
including India, Indonesia, Malaysia, the Philippines, Thailand, and Vietnam.

From its discovery until 2007, there were only 14 confirmed human cases of
Zika virus infection from Africa and Southeast Asia.[71]
[25]

Micronesia, 2007
Main article: 2007 Yap Islands Zika virus outbreak
In April 2007, the first outbreak outside of Africa and Asia occurred on the island
of Yap in the Federated States of Micronesia, characterized by rash,
conjunctivitis, and arthralgia, which was initially thought to be
dengue, chikungunya, or Ross River disease.[72] Serum samples from patients in
the acute phase of illness contained RNA of Zika virus. There were 49 confirmed
cases, 59 unconfirmed cases, no hospitalizations, and no deaths.[73]

Oceania, 20132014
This section requires expansion.
(February 2016)

Main article: 20132014 Zika virus outbreaks in Oceania

Between 2013 and 2014, further epidemics occurred in French Polynesia, Easter
Island, the Cook Islands, and New Caledonia.[5]

Americas, 2015present
Main article: Zika virus outbreak (2015present)
As of early 2016, a widespread outbreak of Zika virus is ongoing, primarily in
the Americas. The outbreak began in April 2015 in Brazil, and has spread to
other countries in South America, Central America, Mexico, and the Caribbean.
In January 2016, the World Health Organization (WHO) said the virus was likely
to spread throughout most of the Americas by the end of the year;[74] and in
February 2016, the WHO declared the cluster of microcephaly and Guillain
Barr syndrome cases reported in Brazil strongly suspected to be associated
with the Zika virus outbreak a Public Health Emergency of International
Concern.[75][76][77][78] It is estimated that 1.5 million people have been infected by Zika
virus in Brazil,[79] with over 3,500 cases of microcephaly reported between
October 2015 and January 2016.[80]
A number of countries have issued travel warnings, and the outbreak is expected
to significantly impact the tourism industry.[78][81] Several countries have taken the
unusual step of advising their citizens to delay pregnancy until more is known
about the virus and its impact on fetal development.[16]

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