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Lecture 38

BISC300 Lecture 38: Zika Virus Lecture Notes

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Biological Sciences
Cooper Carlton

4/24Zika Virus ZIKV • Family: Flaviviridae, Genus: Flavivirus • Genus includes, West Nile virus, dengue virus, yellow fever virus, Japanese encephalitis, and tick-borne encephalitis virus • Nonsegmented, positive sense, ssRNA virus • Enveloped, icosahedral virus ZIKV Replication: • Attachment / Fusion & release / translate (ssRNA polyprotein) / ssRNA  dsRNA / Virus assembly / tansfer / mature viron / release • Attachment of the viral envelope protein E to host receptors mediates internalization into the host cell by apoptotic mimicry • Fusion of virus membrane with host endosomal membrane. RNA genome is released into the cytoplasm. • 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) • Replication takes place at the surface of endoplasmic reticulum in cytoplasmic viral factories. A dsRNA genome is synthesized from the genomic ssRNA(+) • The dsRNA genome is transcribed/replicated there by providing viral mRNAs/new ssRNA(+) genomes • Virus assembly occurs at the endoplasmic reticulum. The virion buds via the host ESCRT complexes at the endoplasmic reticulum, is transported to the Golgi apparatus • The prM protein is cleaved in the Golgi, thereby maturing the virion which is fusion competent • Release of new virions by exocytosis. Symptoms: • Lasts several days to a week • Illness usually mild • Red eyes (conjunctivitis) • Fever • Joint Pain • Rash Zika and Guillain-Barré Syndrome • Guillain-Barré syndrome (GBS) is an uncommon sickness of the nervous system in which a person’s own immune system damages the nerve cells, causing muscle weakness, and sometimes, paralysis • The Brazil Ministry of Health has reported an increased number of people who have been infected with Zika virus who also have GBS • GBS is very likely triggered by Zika in a small proportion of infections, much as it is after a variety of other infections • CDC is working with Brazil to study the possibility of a link between Zika and GBS Symptoms of GBS • GBS symptoms include weakness of the arms and legs that is usually the same on both sides of the body. In some cases, the muscles of the face that control eye movement or swallowing may also become weak. In the most serious cases, this muscle weakness can affect breathing, and in some cases a breathing tube is required 2 • These symptoms can last a few weeks or several months. Although most people fully recover from GBS, some people have permanent damage, and in 1 out of 20 cases people have died Causes of GBS • Most people with GBS report a bacterial or viral infection before they have GBS symptoms. Rarely, vaccination has also been associated with the onset of GBS (i.e., 1976 Swine influenza vaccine). In many cases, however, because the onset of GBS appears to occur days to weeks after a sickness is over, it is difficult to say whether the illness/vaccination “caused” GBS. GBS is rare • An estimated 3,000 to 6,000 people, or 1-2 cases for every 100,000 people, develop GBS each year in the US. Most cases of GBS tend to occur for no known reason, and true “clusters” of cases of GBS are very unusual. Zika - Emergence • Human-dominated environment, urban crowding, constant international travel, and other human behaviors combined with human-caused microperturbations in ecologic balance • The most recent emergence is so wide spread and so recent that we don’t have the data yet to say why Zika emerged. Viral sequencing data indicates likely from French Polynesia in 2013. • Many people have begun to discuss climate change and the increase in range of the Aedes mosquitos. Caution is warranted. Brazil has always been a climate conducive to these species. We have tracked the spread of dengue (another flavivirus, Aedes aegypti vector) to human movements and global trade. Diseases now considered tropical were once found much further north. Transmission: Sex CDC: • Zika can be passed through sex from a person with Zika to his or her partners. • Sex includes vaginal, anal, and oral sex and the sharing of sex toys. • Zika can be passed through sex even in a committed relationship. • The timeframes that men and women can pass Zika through sex are different because Zika virus can stay in semen longer than in other body fluids. • Infected People Can Pass Zika Through Sex Even When They Don’t Have Symptoms • Many people infected with Zika virus won’t have symptoms or will only have mild symptoms, and they may not know they have been infected. • Zika can also be passed from a person before their symptoms start, while they have symptoms, and after their symptoms end. Prevention 3 CDC: How to Protect Yourself During Sex • Condoms can reduce the chance of getting Zika from sex. • male and female condoms. • To be effective, condoms should be used from start to finish, every time during vaginal, anal, and oral sex and the sharing of sex toys • Dental dams may also be used for certain types of oral sex (mouth to vagina or mouth to anus). • Not sharing sex toys can also reduce the risk of spreading Zika to sex partners. • Not having sex eliminates the risk of getting Zika from sex. Transmission: From pregnant mother to her fetus • Pregnant women can be infected with Zika virus. The primary way that pregnant women get Zika virus is through the bite of an infected mosquito. • A pregnant woman can pass Zika virus to her fetus. Zika virus can be passed from a pregnant woman to her fetus during pregnancy or at delivery. Transmission: Blood Transfusion • To date, there have been no confirmed transfusion-transmission cases of Zika virus in the United States. However, cases of Zika virus transmission through platelet transfusions have been documented in Brazil. • During the French Polynesian outbreak, 2.8% of blood donors tested positive for Zika and in previous outbreaks, the virus has been found in blood donors. • OnAugust26,2016,FDAissuedrevisedguidance,recommendingthatbloodcentersinallstates and U.S. territories screen individual units of donated whole blood and blood components with a blood screening test authorized for use by FDA under an investigational new drug (IND) application, or with a licensed test when available. Alternatively, and FDA- approved pathogen- reduction device may be used for plasma and certain platelet products. Zika Virus Blood Screening • Blood donor screening on the basis of a questionnaire, without a laboratory test, is insufficient for identifying Zika-infected donors in areas with active mosquito-borne transmission of Zika virus due to the high rate of asymptomatic infection. • Although there is no FDA-licensed test for Zika virus, testing for Zik
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