BELAJAR TENTANG PROFIL Flaviviridae virus family DAN Flavivirus genus DALAM Zika virus (ZIKV)

Berikut merupakan kutipan ilmiah Mikrobiologi Kedokteran yang bermanfaat sehingga disusun dan digunakan sebagai referensi pribadi.

Perpustakaan Keluarga : Helmut Todo Tua Simamora dan dr. Olga Y.V Hutapea

A U.S. vector biologist appears to have accidentally written virological history simply by having sex with his wife after returning from a field trip to Senegal. A study just released in Emerging Infectious Diseases suggests that the researcher, Brian Foy of Colorado State University in Fort Collins, passed to his wife the Zika virus, an obscure pathogen that causes joint pains and extreme fatigue. If so, it would be the first documented case of sexual transmission of an insect-borne disease.

Foy is the first author of the paper, which describes three anonymous patients. But in an interview with Science, he confirmed that he is the anonymous "patient 1"; his Ph.D. student Kevin Kobylinski, who accompanied him on the trip to Senegal and also got sick, is "patient 2." Foy's wife, Joy Chilson Foy, a nurse at the Poudre Valley Hospital in Fort Collins, is "patient 3"; she is also a co-author of the paper.

Exactly what happened when Foy and Kobylinski returned from Senegal on 24 August 2008 has remained a mystery for years. As part of their research on malaria, the scientists had been collecting mosquitoes in a southeastern village called Bandafassi, where they were often bitten. About 5 days after their return, both researchers got sick. Both had a rash on their torso, extreme fatigue, headaches, and swollen and painful wrists, knees, and ankles. Foy also had symptoms of prostatitis, including painful urination, and he and his wife noticed what looked like blood in his semen, according to the paper.

On 3 September, Foy's wife's fell ill as well, with malaise, chills, extreme headache, hypersensitivity to light, and muscle pains. The couple's four children remained healthy. The symptoms started receding within about a week in all three patients, although the joint pains lingered.

The scientists suspected they were infected through one of their many mosquito bites but were stumped as to the pathogen. So were several laboratories, including the U.S. Centers for Disease Control and Prevention (CDC), whose lab for insect-borne diseases is in Fort Collins. Antibody tests on serum samples from the two scientists tested positive for dengue, a viral disease that might have explained the symptoms, but samples from Chilson Foy came back negative. "Eventually, the CDC said, 'We think you had dengue, but we don't know what your wife had,' " says Foy, who decided to keep samples from all three in the freezer.

The mystery might never have been solved if Kobylinski hadn't gone out for a few beers with Andrew Haddow, a medical entomologist at the University of Texas Medical Branch (UTMB) at Galveston, during another trip to Senegal more than a year later. Haddow, who studies how pathogens survive in the jungle and emerge when humans encroach, had a great personal interest in Zika: His grandfather, Alexander Haddow, was one of three scientists who had isolated the virus from a rhesus monkey in the Zika Forest near Entebbe, Uganda, in 1947 and described it in a paper in 1952. "I read all of my grandfather's papers, so that stuff really interests me," Haddow says.

Zika, he speculated, might account for the trio's symptoms—even though "it was just a hunch." After Kobylinski returned home in December 2009 and told Foy about the encounter, they decided to send the samples to Haddow, who asked his UTMB colleague Robert Tesh, a veteran virologist, to run a battery of tests, including one for the Zika virus. Sure enough, all three samples had antibodies to the virus. "Then it all fell into place," Foy says. The dengue antibodies were a red herring, he says: both researchers had been vaccinated for the yellow fever virus, which is closely related to dengue; antibodies against these viruses often cross-react.

There is no direct evidence that Foy's wife was infected through sexual contact, but the circumstantial evidence is strong. It's very unlikely that she was infected by a bite by a mosquito that first bit her husband; the three tropical Aedes mosquito species known to transmit Zika don't live in northern Colorado, and moreover, the virus has to complete a 2-week life cycle within the insect before it can infect the next human; Foy's wife fell ill just 9 days after his return. And yes, as the paper puts it, "patients 1 and 3 reported having vaginal sexual intercourse in the days after patient 1 returned home but before the onset of his clinical illness." ("My wife wasn't happy with what happened afterwards," Foy adds.)

Not much is known about the Zika virus, which is found in many parts of Africa and Southeast Asia. Researchers from the Pasteur Institute in Dakar reported in 1993 that it occurs in southeastern Senegal, where Foy and Kobylinski work, but it's unknown how often it causes disease. Most cases are never reported or are mistaken for dengue, a much more widespread disease, Haddow says. In fact, only 14 Zika cases had ever been described in the medical literature until an explosive outbreak occurred in 2007 on Yap, an island in the Federated States of Micronesia, where it had never been seen before. An extensive investigation of that epidemic by CDC concluded that 73% of the population was infected, an impressive number that suddenly made Zika an emerging pathogen to watch.

Foy and his co-authors believe sexual transmission of a mosquito-borne virus has never been reported before, although there were hints from the literature that it might be possible. Boars experimentally infected with the Japanese encephalitis virus, for instance, shed the virus in their semen, and female pigs artificially inseminated with it become infected.

Scientists already knew that many insect-borne pathogens can be transmitted orally as well, says medical entomologist Paul Reiter of the Pasteur Institute in Paris. So even if it hasn't been documented before, it's not a big surprise that infected semen deposited inside the vagina could cause an infection, he says.

What's still unclear is how important sexual transmission is in Zika's epidemiology. Haddow believes it plays a very minor role at best and that the vast majority of cases occur through mosquito bites. Yet a few data points from the Yap outbreak hint that sexual transmission may have played a role, Foy says. The population aged between 30 and 59 was hardest hit, and among women, the so-called attack rate—the percentage of people who get sick—was almost 50% higher than among men. (With most sexually transmitted infections, vaginal intercourse poses a higher risk of infection for women.) But there could be other explanations for that as well; Foy says he's interested in studying the issue.

Haddow is doing more research on Zika as well. Although he never really knew his grandfather, he says that stories about his career inspired him to become a virus hunter, and helping solve the Fort Collins riddle, he adds, was "a very good feeling. ... I think my grandfather would have been happy too."

Flaviviridae

VIRION

A Viral Biorealm page on the family Flaviviridae

Baltimore Classification

Higher order taxa

Viruses; ssRNA positive-strand viruses, no DNA stage; Flaviviridae

Genera

Flavivirus, Pestivirus, Hepacivirus

Description and Significance

Flaviviridae contains a myriad of viruses that cause disease in humans. Flaviviridae has a total of 69 pathogens in its rank. The family gets its name from Yellow Fever virus, a type virus of Flaviviridae; flavus means yellow in Latin.

The Flavivirus genus contains several nasty critters that include yellow fever virus, dengue fever virus, and Japanese encephalitis (JE) virus. The pestivirus genus has three serotypes of bovine viral diarrhea, but no human pathogens are yet known. Genus Hepacivirus consists of hepatitis C virus and its relatives. (source: Stanford.edu)

Genome Structure

The genome of Flaviviridae is not segmented and contains a single molecule of linear positive-sense, single-stranded RNA. The complete genome is 9500-12500 nucleotides long. The 5'-end of the genome has a methylated nucleotide cap, or genome-linked protein (VPg). The 3'- terminus has no poly (A) tract but the poly (A) tract is present in some strains of tick-born encephalitis complex of flaviviruses. (source: ICTV dB Descriptions)

Virion Structure of a Flaviviridae

The virions of flaviviridae consist of an envelope and a nucleocapsid. The virus capsid is enveloped. The virions ar spherical to pleomorphic and measure 40-60 nm in diameter. There are small spikes surrounded by a prominent fringe that make up the surface projections. The capsid is round and exhibits a polyhedral symmetry. The core is isometric and has a diameter of 25-30 nm. The capsids can be penetrated by stain and some appear dark in the center. (source: ICTV dB Descriptions)

Reproduction Cycle of a Flaviviridae in a Host Cell

Viral Ecology & Pathology

Many species of Flaviviridae can replicate in both mammalian and insect cells. They can survive for long periods in hosts such as ticks by replicating in this host without damage to the insect.

Flaviviridae viruses produce a wide range of diseases including fever, arthralgia, rash, haemorrhagic fever and encephalitis. The outcome of infection is influenced by both the virus and a number of host-specific factors like age, sex, genetic susceptibility and preexposure to same or related agent.

LinkOut	Subject	LinkOut Provider
Flaviviridae	taxonomy/phylogenetic	Encyclopedia of life
Flaviviridae	taxonomy/phylogenetic	International Committee on Taxonomy of Viruses
Flaviviridae	taxonomy/phylogenetic	World Register of Marine Species
Wikipedia	taxonomy/phylogenetic	iPhylo

Enveloped, spherical, about 50 nm in diameter. The surface proteins are arranged in an icosahedral-like symmetry.
Source: Zhang et al

GENOME

Monopartite, linear, ssRNA(+) genome of about 9.7-12 kb. The genome 3’ terminus is not polyadenylated but forms a loop structure. The 5’ end has a methylated nucleotide cap (to allow translation) or a genome-linked protein (VPg).

GENE EXPRESSION

The virion RNA is infectious and serves as both the genome and the viral messenger RNA. The whole genome is translated into a polyprotein, which is processed co- and post-translationally by host and viral proteases.

REPLICATION

CYTOPLASMIC

1. Attachement of the viral envelope protein E to host receptors mediates internalization into the host cell by clathrin-mediated endocytosis or by apoptotic mimicry
2. Fusion of virus membrane with host endosomal membrane. RNA genome is released into the cytoplasm.
3. The positive-sense genomic ssRNA is translated into a polyprotein, which is cleaved into all structural and non structural proteins (to yield the replication proteins).
4. Replication takes place at the surface of endoplasmic reticulum in cytoplasmic viral factories. A dsRNA genome is synthesized from the genomic ssRNA(+).
5. The dsRNA genome is transcribed/replicated thereby providing viral mRNAs/new ssRNA(+) genomes.
6. Virus assembly occurs at the endoplasmic reticulum and seems to be facilitated by theviral ionic channel p7. The virion buds via the host ESCRT complexes at the endoplasmic reticulum, is transported to the Golgi apparatus.
7. Release of new virions by exocytosis.

TAXONOMY

Group IV: ssRNA positive-strand viruses

Family:	Flaviridae
Genus:	Flavivirus Hepacivirus Pegivirus Pestivirus

SPECIES

Type:	Hepatitis C virus (HCV) Yellow fever virus (YFV) Bovine diarrhea virus 1 (BVDV-1)
Main:	Dengue virus (DENV)

Flaviviridae is a family of viruses. Humans and other mammals serve as natural hosts. They are primarily spread through arthropod vectors (mainly ticks and mosquitoes). The family gets its name from the Yellow Fever virus, the type virus ofFlaviviridae; flavus means yellow in Latin. (Yellow fever in turn was named because of its propensity to cause jaundice in victims.)^[1] There are currently over 100 species in this family, divided among four genera. Diseases associated with this family include: hepaciviruses: hepatitis; pestiviruses: hemorrhagic syndromes, abortion, fatal mucosal disease; flavivirus: hemorrhagic fever, encephalitis.^[2][3]

Flaviviridae
Virus classification
Group:	Group IV ((+)ssRNA)
Family:	Flaviviridae
Genera
Hepacivirus Flavivirus Pegivirus Pestivirus

Taxonomy

• Genus Flavivirus (type species Yellow fever virus, others include West Nile virus, Dengue Fever and Zika virus)—contains 67 identified human and animal viruses
• Genus Hepacivirus (type species Hepatitis C virus,^[4] also includes GB virus B)
• Genus Pegivirus (includes GB virus A, GB virus C, and GB virus D)
• Genus Pestivirus (type species bovine viral diarrhea virus, others include classical swine fever or hog cholera)—contains viruses infecting non-human mammals

Group: ssRNA(+)

Order: Unassigned

Genome

Flaviviridae have monopartite, linear, single-stranded RNA genomes of positive polarity, 9.6 to 12.3 kilobase in length. The 5'-termini of flaviviruses carry amethylated nucleotide cap, while other members of this family are uncapped and encode an internal ribosome entry site.

Virion structure

Virus particles are enveloped, with icosahedral and spherical geometries, about 40–60 nm in diameter.^[2]

Genus	Structure	Symmetry	Capsid	Genomic Arrangement	Genomic Segmentation
Hepacivirus	Icosahedral-like	Pseudo T=3	Enveloped	Linear	Monopartite
Flavivirus	Icosahedral-like	Pseudo T=3	Enveloped	Linear	Monopartite
Pegivirus	Icosahedral-like	Pseudo T=3	Enveloped	Linear	Monopartite
Pestivirus	Icosahedral-like	Pseudo T=3	Enveloped	Linear	Monopartite

Life Cycle

Viral replication is cytoplasmic. Entry into the host cell is achieved by attachment of the viral envelope protein E to host receptors, which mediates clathrin-mediated endocytosis. Replication follows the positive stranded RNA virus replication model. Positive stranded RNA virus transcription is the method of transcription. Translation takes place by viral initiation. The virus exits the host cell by budding. Humans and mammals serve as the natural host. The virus is transmitted via a vector (ticks and mosquitoes).^[2]

Genus	Host Details	Tissue Tropism	Entry Details	Release Details	Replication Site	Assembly Site	Transmission
Hepacivirus	Humans	Epithelium: skin; epithelium: kidney; epithelium: intestine; epithelium: testes	Clathrin-mediated endocytosis	Secretion	Cytoplasm	Cytoplasm	Sex; blood
Flavivirus	Humans; mammals; mosquitoes; ticks	Epithelium: skin; epithelium: kidney; epithelium: intestine; epithelium: testes	Clathrin-mediated endocytosis	Secretion	Cytoplasm	Cytoplasm	Zoonosis; arthropod bite
Pegivirus	Mammals	None	Clathrin-mediated endocytosis	Secretion	Cytoplasm	Cytoplasm	Unknown
Pestivirus	Mammals	None	Clathrin-mediated endocytosis	Secretion	Cytoplasm	Cytoplasm	Vertical: parental

Clinical importance

Major diseases caused by the Flaviviridae family include:

• Dengue fever
• Japanese encephalitis
• Kyasanur Forest disease
• Murray Valley encephalitis
• St. Louis encephalitis
• Tick-borne encephalitis
• West Nile encephalitis
• Yellow fever
• Hepatitis C Virus Infection
• Zika Virus

Entrez records
Database name	Subtree links	Direct links
Nucleotide	248,497	1
Protein	199,767	1
Structure	607	-
Genome	78	-
Popset	2,295	6
Domains	31	12
GEO Datasets	210	4
PubMed Central	30,805	3,288
Gene	210	-
SRA Experiments	2,291	1
Probe	1,189	-
Assembly	87	-
Bio Project	51	1
Bio Sample	2,944	1
PubChem BioAssay	3,632	-
Taxonomy	918	1

Flaviviridae Genome Statistics
Genera	4
Species	233
Strains	175,191
3D Protein Structures (PDB)	1,450
Experimentally Determined Epitopes (IEDB)	73,843
Genomes with Clinical Metadata (NIAID GSCID, manual curation)	2,749
Mature Peptides	223,852
Sequence Features with Variant Types	842
Proteins with Predicted Epitopes	393,140
Flavivirus Strains with Predicted Genotypes	107,679
Total Genomes	244,847
Complete Genomes	8,903
Proteins	599,042

Flaviviridae

Taxonomy ID: 11050

Inherited blast name: viruses

Rank: family

Genetic code: Translation table 1 (Standard)

Other names:

synonym:

Flavivirus (arbovirus group B)

Lineage( full )

Viruses; ssRNA viruses; ssRNA positive-strand viruses, no DNA stage

Genome Information

Trace records (raw single-pass reads of DNA sequence)
Sequencing Center Name
Record counts per type
RT-PCR	ALL
NADC - United States Department of Agriculture, Agricultural Research Service, National Animal Disease Center
4,086	4,086
Totals per type
4,086	4,086

External Information Resources (NCBI LinkOut)

LinkOut	Subject	LinkOut Provider
Flaviviridae	taxonomy/phylogenetic	Encyclopedia of life
Flaviviridae	taxonomy/phylogenetic	International Committee on Taxonomy of Viruses
Flaviviridae	taxonomy/phylogenetic	World Register of Marine Species
Wikipedia	taxonomy/phylogenetic	iPhylo

Flaviviridae Taxonomy

Family:

Flaviviridae

(4 Genera - 8903 complete genomes)

Genus:

Flavivirus

(53 Species - 6013 complete genomes)

Genus:

Hepacivirus

(2 Species - 2410 complete genomes)

Genus:

Pegivirus

(1 Species - 165 complete genomes)

Genus:

Pestivirus

(5 Species - 275 complete genomes)

Genus:

Unclassified Flaviviridae

(13 Species - 40 complete genomes)

Just last summer, Zika seemed too trivial for anyone to bother developing countermeasures. The mosquito-borne virus was racing through countries in the Southern Hemisphere, but, at worst, it appeared to cause a mild fever and rash. No longer: On 1 February the World Health Organization (WHO) declared the “extraordinary” cluster of microcephaly and other neurological complications that have now been linked to Zika a public health emergency of international concern. And vaccinemakers, big and small, have begun the race to head it off. They have a good shot at success, several experts say—cautioning that vaccine development requires years of testing.

Isolated in 1947, Zika first caused serious concern in May 2015 after it arrived in South America and suspicions grew that infection during pregnancy could cause brain-damaging microcephaly in babies. The link, WHO Director-General Margaret Chan stresses, is “strongly suspected though not yet scientifically proven”—as is a potential connection to Guillain-Barré, which causes a temporary paralysis in adults. With viral spread increasing, a vaccine is now a top priority.

Vaccine pioneer Stanley Plotkin of the University of Pennsylvania predicts “a straightforward developmental pathway” for a vaccine. He notes that Zika belongs to the flavivirus family, and vaccines exist for several of its relatives, including dengue, yellow fever, and Japanese encephalitis. “I don’t see any technical issues such as the ones that obviously exist for vaccines against HIV, tuberculosis, and many other agents,” says Plotkin, who consults with several vaccinemakers.

Still, “there are many puzzles,” says Thomas Monath, a virologist who studied Zika in wild monkeys in Nigeria and is now the chief scientific officer at NewLink Genetics in Devens, Massachusetts, whose team helped develop a promising Ebola vaccine. For Zika, one unknown is whether infection leads to lifelong protection—a key feature of diseases for which vaccines are most effective, such as yellow fever. Another question is whether natural or vaccine-induced immunity against other related viruses—particularly yellow fever—could offer a measure of “cross protection,” which might confuse efforts to evaluate Zika vaccines. Nor have researchers yet established a much-needed monkey model to enable comparisons of candidate vaccines.

Approaches have proliferated. Monath, who has developed vaccines against several flaviviruses, says NewLink will pursue a traditional strategy that inactivates, or kills, the virus with a chemical so it cannot replicate in the body. He thinks an inactivated vaccine has the best chance of winning regulatory approval for a product that pregnant women might use.

At the nonprofit Butantan Institute in São Paulo, Brazil, immunologist and director Jorge Kalil is betting that a weakened, live vaccine can be safe and potentially more effective than killed virus. His team plans to exploit a technology that researchers at the U.S. National Institute of Allergy and Infectious Diseases (NIAID) used to make a dengue vaccine, which Butantan licensed and is now testing in an efficacy trial. To weaken that virus, researchers deleted genes so it can copy itself but not cause disease. “Perhaps we can attenuate the Zika virus by using the same deletions of the same sites,” Kalil says, noting that Butantan likely would partner with NIAID to develop its vaccine. The Brazilian institute has a key advantage: Unlike almost every other institution in the world that does vaccine research, it has an industrial-scale manufacturing plant—last year the institute cranked out 40 million doses of influenza vaccine—so it might be able to supply enough product for Brazil without needing help from big pharma.

NIAID Director Anthony Fauci says his institute has a “head start” with a different technology it used to make an experimental vaccine for West Nile, another flavivirus. The manufacturing process begins with a circular “plasmid” of DNA that holds key viral genes. When it is inserted into bacterial cells, they produce “viruslike particles” that can serve as an inactivated vaccine, because they cannot copy themselves. (The West Nile vaccine worked well in early human studies, but NIAID could not find a commercial partner to take it forward.)

Inovio Pharmaceuticals of Plymouth Meeting, Pennsylvania, boasts it already has an experimental Zika vaccine containing nothing more than a plasmid made of Zika genes. With the help of an electrical zap on the skin, the plasmid goes directly into human cells, which make Zika proteins that stimulate the immune system. CEO Jerome Kim says his team already has begun tests in mice. But although researchers can quickly make such simple DNA vaccines, they have lost their luster over the past 20 years because they have not triggered strong immune responses against other diseases. “There are people very knowledgeable in the field who have lost faith in this technology,” Kim concedes. “I want to prove to the field that this technology is viable and perhaps the best option for these types of outbreaks.”

The small Jenner Institute in Oxford, U.K., is putting the Zika surface protein into harmless chimpanzee adenoviruses, which serve as a “vector” —an approach similar to one used in GSK’s Ebola vaccine, which was tested during the West African epidemic. Vaccinemakers Protein Sciences of Meriden, Connecticut, and Hawaii Biotech of Honolulu—which both specialize in producing viral proteins in insect cell lines—also have projects underway.

Predicting when a vaccine will come to market is a mug’s game, but NIAID’s Fauci thinks animal studies could be completed in a few months and small human studies to evaluate safety and immune responses could begin by the end of 2016. Even if a promising candidate surfaces, large-scale efficacy trials are probably years away, he says. Getting a vaccine approved and supplying millions of doses could take the resources of a major manufacturer. Of the four big pharma companies that make vaccines, only Sanofi Pasteur of Lyon, France—makers of three flavivirus vaccines—has launched a Zika program, though the others say they are watching the field closely.

As a stopgap measure, Kalil says Butantan hopes to produce a protective serum for pregnant women, which the institute already makes for several diseases, by injecting Zika virus into horses and harvesting the antibodies the animals make. “This would take a little over a year,” Kalil says. “That’s the best timeline—if you’re very, very optimistic.”

Increasingly strong links between the spread of Zika virus and microcephaly in newborns led the World Health Organization (WHO) today to declare a Public Health Emergency of International Concern.

WHO Director-General Margaret Chan in Geneva, Switzerland, made this declaration upon the advice of a committee of 18 experts and advisers, who she said “agree that a causal relationship between the Zika infection during pregnancy and microcephaly is strongly suspected though not yet scientifically proven.” Zika, a mosquito-borne virus, is currently spreading through 24 countries in Latin America and the Caribbean, plus Cape Verde, an island off West Africa. Chan noted that there was “a particularly strong association in time and in space” between the arrival of the virus and the detection of microcephaly and other neurological disorders. Although Brazil has had more than 4000 suspected cases of microcephaly, it has confirmed only 270 cases of this brain-damaging condition in children born to mothers who had evidence of having been infected with the virus.

Although Brazil is the only country to report a spike in microcephaly during the current outbreak, French Polynesia in 2014 saw a rise in this rare disorder concurrent with viral spread, Chan said. Brazil, El Salvador, and French Polynesia also suspect Zika virus may have led to increased cases of a neurological disorder in adults called Guillain-Barre syndrome that causes temporary paralysis. “The committee advised that the cluster of microcephaly and other neurological complications constitute an extraordinary event and public threat to other parts of world,” Chan explained. She was careful to note that her declaration of concern focused on these clusters and not the spread of the virus itself, which causes no symptoms in 80% of people it infects, and a short-lived rash and fever in the other 20%.

Many criticized WHO for not sounding this alarm when the Ebola outbreak surfaced in 2014. “It was a very difficult decision to discern between what is a Public Health Emergency of International Concern and what should be precautionary measures because of a possible relation between Zika and these clusters,” explained the chair of the committee, epidemiologist David Heymann of the London School of Hygiene & Tropical Medicine.

Chan suggested that pregnant women not living in Zika-affected countries may want to delay travel to those areas but did not issue a formal travel alert for them, as the U.S. Centers for Disease Control and Prevention has done. Chan stressed that “the committee found no public health justification for restrictions on travel or trade to prevent the spread of Zika virus.” Many countries ignored similar recommendations during the Ebola epidemic in West Africa and imposed what WHO saw as unnecessary and even counterproductive travel and trade restrictions.

In tandem with the declaration, the committee made two major recommendations: Standardize surveillance for microcephaly and other neurological disorders in places where Zika is spreading, and intensify research to discern whether the clusters of cases are truly linked to the virus.

“There is an urgent need to do a lot more work,” Chan said. She also stressed that the world had to step up mosquito control efforts, surveillance of Zika, and efforts to develop a vaccine. “Can you imagine if we do not do all this work now and wait until the scientific evidence comes out?” she asked.

Lawrence Gostin, a lawyer who specializes in global health law at Georgetown University in Washington, D.C., supports  the declaration but stated in a press release that WHO needs to spell out more explicitly how it intends to respond. “Margaret Chan was silent on what strategy the organization will take on the ground to control Zika and how she will mobilize the major funding needed for surveillance, mosquito control, and critical research,” Gostin contended. “Without a clear strategy and ample resources, sounding an alert is simply not enough.”

Zika has been sexually transmitted in Texas, the Centers for Disease Control and Prevention said Tuesday. It is the first known case of the virus being locally acquired in the continental United States in the current outbreak.

The case, announced by Dallas County health officials, involved a patient who had sex with someone who had recently returned from Venezuela infected with the mosquito-borne virus.

In a statement to CNN, the CDC said it confirmed the test results showing Zika present in the blood of a "nontraveler in the continental United States." They stressed that there was no risk to a developing fetus in this instance.

Based on that, the CDC says it will soon provide guidance on sexual transmission, with a "focus on the male sexual partners of women who are or who may be pregnant."

Earlier Tuesday, CDC Director Tom Frieden told CNN's Chief Medical Correspondent Sanjay Gupta: "There have been isolated cases of spread through blood transfusion or sexual contact and that's not very surprising. The virus is in the blood for about a week. How long it would remain in the semen is something that needs to be studied and we're working on that now."

Frieden added that studies on sexual transmission are not easy studies to do, but the CDC is continuing to explore that avenue of transmission. "What we know is the vast majority of spread is going to be from mosquitoes," Frieden added. "The bottom line is mosquitoes are the real culprit here."

The CDC said it will provide more guidance as more information on sexual transmission is learned, but in the meantime, "Sexual partners can protect each other by using condoms to prevent spreading sexually transmitted infections. People who have Zika virus infection can protect others by preventing additional mosquito bites."

History of sexual transmission

Before this case, there have been only two documented cases linking Zika to sex. During the 2013 Zika outbreak in French Polynesia, semen and urine samples from a 44-year-old Tahitian man tested positive for Zika even when blood samples did not. Five years before that, in 2008, a Colorado microbiologist named Brian Foy contracted Zika after travel to Senegal; his wife came down with the disease a few days later even though she had not left northern Colorado and was not exposed to any mosquitoes carrying the virus.

In addition, the CDC said there have been documented cases of virus transmission during labor, blood transfusion and laboratory exposure. While Zika has been found in breast milk, it's not yet confirmed it can be passed to a baby through nursing.

An emergency of international concern

Zika is prompting worldwide concern because of an alarming connection to a neurological birth disorder and the rapid spread of the virus across the globe.

The Zika virus, transmitted by the aggressive Aedes aegypti mosquito, has now spread to at least 24 countries. The WHO estimates 3 million to 4 million people across the Americas will be infected with the virus in the next year. The Centers for Disease Control and Prevention is warning pregnant women against travel to those areas; health officials in several of those countries are telling female citizens to avoid becoming pregnant, in some cases for up to two years.

Five things you need to know about Zika

The virus is linked to an alarming spike in babies born with abnormally small heads -- a condition called microcephaly -- in Brazil and French Polynesia.

Reports of a serious neurological condition, called Guillain-Barre Syndrome, that can lead to paralysis, have also risen in areas where the virus has been reported. Health officials have specifically seen clusters of this in El Salvador, Brazil and French Polynesia, according to WHO's Dr. Bruce Aylward.

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