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About viruses and viral disease

zika virus

Zika virus infection of the nervous system

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FlavivirusEvidence is mounting that Zika virus is neurotropic (able to infect cells of the nervous system) and neurovirulent (causes disease of the nervous system) in humans.

The most recent evidence comes from a case report of an 81 year old French man who developed meninogoencephalitis 10 days after returning from a 4 week cruise to New Caledonia, Vanuatu, Solomon Islands, and New Zealand (meningoencephalitis is infection of the meninges - the membranes that cover the brain - and the brain). His symptoms included fever, coma, paralysis, and a transient rash. A PCR test revealed Zika virus genomes in the cerebrospinal fluid, and infectious virus was recovered after applying the CSF to Vero cells in culture.

A second case report concerns a 15 year old girl in Guadeloupe who developed left hemiparesis (weakness of one side of the body), left arm pain, frontal headache, and acute lower back pain. After admission she developed dysuria (difficulty urinating) that required catheterization. PCR revealed the presence of Zika virus genomes in her serum, urine, and cerebrospinal fluid; other bacterial and viral infections were ruled out.

Until very recently Zika virus was believed to cause a benign infection comprising rash, fever, joint pain, red eyes, and headache. There is now strong evidence that the virus can cause congential birth defects, and growing evidence that the virus is neurotropic and neurovirulent. Previously the entire Zika virus genome was recovered from brain tissue of an aborted fetus.

Zika virus is classified in the family Flaviviridae, and other members are known to be neurotropic, including West Nile virus, Japanese encephalitis virus, and tick-borne encephalitis virus. West Nile virus infection may lead to acute flaccid paralysis, meningitis, encephalitis, and ocular manifestations. Examination of additional cases of Zika virus infection will be needed to document the full spectrum of illness caused by this virus.

Update: Neurotropism of Zika virus is also indicated by the findings that the virus infects human cortical neural progenitors.

TWiV 379: A mouse divided

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TWiVOn episode #379 of the science show This Week in Virology, Scott Tibbetts joins the TWiVirate to describe his work on the role of a herpesviral nocoding RNA in establishment of peripheral latency, and then we visit two last minute additions to the Zika virus literature.

You can find TWiV #379 at microbe.tv/twiv, or listen below.

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TWiV 378: Herpes plays DUBstep

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TWiVOn episode #378 of the science show This Week in Virology, Greg Smith joins the TWiVirate to reveal how his lab discovered a switch that controls herpesvirus neuroinvasion, and then we visit the week’s news about Zika virus.

You can find TWiV #378 at microbe.tv/twiv, or you may listen below.

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Person to person Zika virus transmission

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FlavivirusThe title of a Eurosurveillance article, “An autochthonous case of Zika due to possible sexual transmission, Florence, Italy, 2014” was written to make the headlines. The title should be “An autochthonous case of Zika due to person to person contact, Florence, Italy, 2014.”

An Italian man returns from a 10 day holiday in Thailand and a day later develops a rash with fever and headache. Within 6 days the rash has subsided. About two weeks later his girlfriend develops a similar disease. As this was 2014 no one looked for Zika virus and both were presumed to have dengue virus infection.

The serum samples taken from the patients were pulled from the freezer after Zika virus becomes a household word in 2015. Both patients’ sera are shown to contain neutralizing antibodies against Zika virus, with a clear rise between samples taken early in illness and after recovery.

Apparently the couple had sex between the time the man’s rash subsided, and the onset of the girlfriend’s symptoms. The authors of the paper conclude that transmission by semen is suggested.

Inexplicably, the authors write:

Other transmission modalities (i.e. direct contact with other bodily fluids) are unlikely to play a role but may not be completely ruled out.

Why is it unlikely that the man had a residual rash, possibly leaking virus, which he then transferred to the woman, perhaps on one or more mucus membranes? This mode of transmission is also known as ‘close contact’ between individuals. I am waiting for a similar case report in which the couple used condoms, yet Zika virus infection was still transmitted.

Like everyone else, the authors are seduced by the possibility of sexual transmission of Zika virus. I have yet to see any clear, convincing evidence of sexual transmission of Zika virus. At worst, the risk is extremely low, although probably not zero, given that Zika virus RNA (not virus) has been found in semen of one individual. Consider these facts and act accordingly.

TWiV 377: Chicken with a side of Zika

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TWiVOn episode #377 of the science show This Week in Virology, the TWiVniks review the past week’s findings on Zika virus and microcephaly, and reveal a chicken protein that provides insight on the restriction of transmission of avian influenza viruses to humans.

You can find TWiV #377 at microbe.tv/twiv, or you can listen below.

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Rubella virus and birth defects

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TogavirusAmidst the fear surrounding Zika virus, remember that there are over 100,000 children born each year with birth defects caused by infection with rubella virus.

The virus
Rubella virus is a member of the Togaviridae family, which also includes chikungunya virus. The genome is a 9.7 kilobase, positive strand RNA enclosed in a capsid and surrounded by a membrane (illustrated; image from ViralZone).

Transmission
Humans are the only natural host and reservoir of rubella virus. The virus is transmitted from human to human by respiratory aerosols.  Upon entry into the upper respiratory tract, the virus replicates in the mucosa and local lymph nodes. Virus then enters the blood and spreads to regional lymph nodes, where it replicates and a second viremia ensues. The incubation period is approximately 14 days, after which virus is shed by respiratory secretions, allowing transmission to other hosts. The second viremia brings virus to the skin, where a rash appears after 14-21 days.

Signs and Symptoms
Rubella is a mild disease associated with low grade fever, swollen lymph nodes and a morbilliform rash. Before a vaccine was available, infection typically occurred between 5-9 years of age. In 1942 the opthalmologist Norman Gregg found that many children with cataracts also had other serious congenital defects. He noticed that an epidemic of congenital cataracts was preceded by a rubella outbreak, and proposed that cataracts and other abnormalities were caused by maternal infection during pregnancy. Eventually other investigators confirmed that rubella virus could cause fetal defects when infection of the mother occurred in the first trimester of pregnancy.

Congenital rubella syndrome (CRS) is the name give to fetal defects caused by rubella virus infection. These include eye manifestations (cataracts, glaucoma, retinitis), congenital heart defects, hearing loss, microcephaly, bone disease, mental retardation, and diabetes. When a pregnant mother is infected early in pregnancy, the virus crosses the placenta and infects most fetal organ systems. No animal models are available to study how the virus causes tissue damage.

In the US during the pre-vaccine era, outbreaks of rubella were routinely accompanied by congenital rubella syndrome. An example is the 1962-65 epidemic of 12.5 million cases of rubella and 20,000 children with congenital abnormalities. The incidence of CRS during rubella outbreaks is 1-2 per 1,000 live births

Rubella infection may also lead to encephalopathy or encephalomyelitis in one case per 6,000 infections. In these cases the virus can be found in cerebrospinal fluid and in the central nervous system.

Control
Rubella virus was the first virus shown to be teratogenic in humans. This discovery hastened development of an infectious, attenuated vaccine, which was licensed in the US in 1969. It is now given to children as part of the MMR vaccine – measles, mumps, and rubella. Its use in the US, and in many other countries, has controlled outbreaks of rubella and eliminated congenital rubella syndrome. The Centers for Disease Control declared in 2005 that endemic congenital rubella syndrome had been eliminated from the US.

Many countries, including much of African, India, Afghanistan, and Pakistan do not include rubella vaccine in routine immunization schedules. As of 2009 less than 40% of the global birth cohort was protected from rubella virus infection. The consequence is that women of childbearing age are susceptible to rubella. In nonepidemic years there are more than 100,000 infants born with CRS every year (source: WHO)

Closing Thoughts
Rubella is an eradicable disease, because the vaccine produces durable immunity, and humans are the only reservoir of the virus. In contrast, Zika virus probably cannot be eradicated, because there is a non-human reservoir of the virus – possibly non-human primates.

Before immunization, rubella was endemic worldwide, with epidemics taking place every 6-9 years, as pools of susceptibles reached a threshold. I wonder if we will see similar behavior with Zika virus, once the initial wave of spread subsides.

Like the outbreak of microcephaly in Brazil, the 100,000 children born annually with congenital rubella syndrome is a tragedy. It’s important to remember that having an effective vaccine does not guarantee control of disease – the vaccine has to be distributed to all who need it.