Tuesday, 5 January 2016

Zika virus briefly...

Update #1. 05JAN2016 2030 AEST
Update #2. 30JAN2016 1430 AEST
Zika (pronounced [zēk′ ə; 1] or zeek-a) virus has been in the news in recent months as it has seemingly spread very quickly from country to country, seemingly at the same time as a rise in cases of an otherwise rare human disease, microcephaly. 

The virus was first grown in the laboratory from samples from a naturally infected sentinel rhesus macaque (monkey) which were placed in cages on variously elevated platforms in the Zika ("overgrown") forest in Uganda in 1947.[18] The virus was not descried in the literature until 1952 although many others from the discoveries in this region were.[18]

I'm new to Zika virus and the study of its spread and disease so I'm on a mission to read up on it. I like to start from the beginning thus I have some of the earliest papers and will gradually read them and share with you any summaries I write up. For now, a general overview of some key bits.

Zika virus causes Zika virus disease (ZVD) or Zika fever - it's that virus versus disease thing that we have for almost all infectious diseases. Zika virus is often abbreviated to ZIKV.

From ViralZone's (www.expasy.org/viralzone,
SIB Swiss Institute of Bioinformatics) excellent
Flaviviridae page at 

ZIKV is a mosquito-borne virus that has an RNA genome (positive sense) and is enveloped by a lipid membrane (with exposed viral bits embedded-see adjacent image) surrounding an icosahedral capsid. Inside the capsid is the genome. This is the same basic structure as that found among other viruses of the family Flaviviridae of which ZIKV is a member; it falls into the genus Flavivirus of the family Flaviviridae to me a bit more precise.

ZIKV replicates in the infected host cell's cytoplasm and first makes a single protein (a polyprotein) which is subsequently cleaved up into different functional peptides.[5,8]

Aedes aegypti mosquito. One of the genus Aedes of 
mosquitoes found to host ZIKV. Other mosquitoes 

Image from CDC via Wikipedia.[9]
Some flaviviruses are borne to us (and other animals) by other arthropods - ticks apart from mosquitoes - infecting us via a virus-laden puncture/bite/injection during which virus is introduced. These viruses are all lumped together under the umbrella term of arthropod-borne viruses or arboviruses

Arboviruses replicate (grow) within the cells of the particular arthropod host, where they are amplified to higher viral loads; for example cells lining the mosquito gut in the case of Dengue virus.[10,11] Some human and animal hosts, as far as we know, cannot amplify the virus enough for it to be sucked back out by and infect the next arthropod that might come along and feed on us - these are called incidental or "dead-end" hosts.[4]

Some flaviviruses have not yet been linked to an insect host. Wikipedia maintains a great long list of flaviviruses, arthropod hosts and their mammalian and avian incidental hosts, as well as those viruses not yet linked to a human or other animal hosts.[4]

Other flaviviruses (members of that genus) you may have heard of include Yellow fever virus (YFV; the prototype virus and from where "flavi", which derives from flavus, meaning yellow/blond/golden in Latin, comes from), Dengue virus (DENV), Japanese encephalitis virus (JEV), Tick-borne encephalitis virus (TBEV), West Nile virus (WNV), St. louis encephalitis virus and Murray valley encephalitis virus (MVEV). But there are 53 species listed in the genus by the International Committee on Taxonomy of Viruses (ICTV) as of 2014 - many of which you won't have heard anything about.[3]

Generally, ZIKV causes a relatively mild illness in a proportion of those infected.[13] Signs and symptoms can include fever, rash, joint (arthralgia) and muscle (myalgia) pain, conjunctivitis, headache and jaundice but with its recent rapid spread - or more rigorous detection - a link is being investigated to a parallel rise in cases of a rare disease, detected at birth or thereafter, called microcephaly. This has been reported in some countries with ZIKV cases, but not from all. At least to date that has been the case - it may change with the new attention this disease and this virus have now attracted. 
Countries and territories with autochthonous transmission.
Epidemiological Week 51 - 2015. PAHO & WHO.[23]

Microcephaly manifests, as the name suggests, as markedly smaller than normal head size and is linked to reduced brain growth in utero or brain development after birth.[6] While a link between microcephaly and viruses is not new, a link (statistical, supported with data) has yet to be found to ZIKV infection.[7] That is not to say a link will not be found, but it is awaiting the required studies. Three instances report ZIKV in amniotic fluid or in newborn tissues and one case of sexual transmission tentatively described.[19,21] Thousands of ZVD cases have reportedly been accruing on a weekly basis in Colombia alone which found its first local (autochthonous) transmission October 2015.[20] The first autochthonous reports of ZIKV infection in the Americas were confirmed in February 2014 on Easter Island, Chile.[22] In May 2015, Brazil reported discovery of its first autochthonous cases and November 2015 saw the first autochthonous circulation reports by El Salvador, Guatemala, Mexico, Paraguay, Suriname, and Venezuela.[22]

Laboratory confirmation of a suspected or probable case can be by detection of ZIKV RNA using RT-PCR in samples from an acutely infected case and by the finding of IgM antibodies 5 or more days after illness onset.[12,13] ZIKV antibody studies must be considered alongside studies of other flaviviruses which may cross-react or non-specifically flare up during infection by another related, or unrelated, virus.[14,15,16,17] The time during which virus remains in the blood may only be 3 to 5 days.[13]

But other infections can look just like ZVD including:[12]

  • dengue viruses
  • leptospirosis
  • malaria
  • rickettsia
  • group A streptococcus
  • rubella virus
  • measles virus
  • parvovirus
  • enterovirus
  • adenovirus
  • Chikungunya virus
  • Mayaro virus
  • Ross River virus
  • Barmah Forest virus
  • O’nyong-nyong
  • Sindbis viruses
So you can see that a lot of work, time and money is required for a lab asked to confirm the disease, rather than a specific viral infection.

No specific antiviral or vaccine exists for ZIKV infection - or most other viral infections.

  1. http://wwwnc.cdc.gov/eid/article/20/6/et-2006_article
  2. http://viralzone.expasy.org/all_by_species/43.html
  3. http://www.ictvonline.org/taxonomyHistory.asp?taxnode_id=20141996&taxa_name=Flavivirus
  4. https://en.wikipedia.org/wiki/Flavivirus
  5. http://web.stanford.edu/group/virus/flavi/2008/flavi.html
  6. http://www.mayoclinic.org/diseases-conditions/microcephaly/basics/definition/con-20034823
  7. http://www.childrenshospital.org/conditions-and-treatments/conditions/microcephaly/symptoms-and-causes
  8. http://viralzone.expasy.org/all_by_protein/24.html
  9. https://commons.wikimedia.org/wiki/File:Aedes_aegypti_CDC-Gathany.jpg
  10. http://www.sciencedirect.com/science/article/pii/S0042682207006642
  11. http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0001385
  12. http://www.cdc.gov/zika/hc-providers/clinicalevaluation.html
  13. http://ecdc.europa.eu/en/healthtopics/zika_virus_infection/factsheet-health-professionals/Pages/factsheet_health_professionals.aspx
  14. http://www.cdc.gov/westnile/healthcareproviders/healthcareproviders-diagnostic.html
  15. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2732478/
  16. https://books.google.com.au/books?id=73pYBAAAQBAJ&pg=PA1158&lpg=PA1158&dq=flavivirus+infection+triggers+heterologous+antibody&source=bl&ots=UYgmkBSso3&sig=CV1uAEb5NZTGfhD-hd0v6EZ7P4g&hl=en&sa=X&ved=0ahUKEwi8idCd0ZHKAhUMkZQKHXMnBNgQ6AEIOzAD#v=onepage&q=flavivirus%20infection%20triggers%20heterologous%20antibody&f=false
  17. https://books.google.com.au/books?id=BseNCgAAQBAJ&pg=PA1898&lpg=PA1898&dq=flavivirus+infection+triggers+heterologous+antibody&source=bl&ots=0JKxv695TR&sig=hvvhStq7BABzIKhzecMhFRW50cg&hl=en&sa=X&ved=0ahUKEwi8idCd0ZHKAhUMkZQKHXMnBNgQ6AEINjAC#v=onepage&q=flavivirus%20infection%20triggers%20heterologous%20antibody&f=false
  18. Zika virus. I. Isolations and serological specificity.
    Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20.
  19. http://www.forbes.com/sites/judystone/2016/01/04/zika-coming-to-america-through-mosquitoes-travel-and-sex/
  20. http://outbreaknewstoday.com/colombia-averaging-more-than-1000-zika-cases-weekly-for-the-past-month-54367/
  21. http://wwwnc.cdc.gov/eid/article/21/2/14-1363_article
  22. http://www.paho.org/Hq/index.php?option=com_docman&task=doc_download&Itemid=&gid=32405&lang=en
  23. http://www.paho.org/hq/images/stories/AD/HSD/IR/Viral_Diseases/Zika-Virus/2015-cha-autoch-human-cases-zika-virus-ew-51.jpg
  1. Grammatical reference and additional location details
  2. Fixed some reference errors