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Zika virus: a New Year update

The Zika virus (ZIKV) is a mosquito-borne virus originally discovered in the Zika Forest area in Uganda in 1947. It was not considered a relevant pathogen for humans until the outbreaks of fever illness that occurred in the Pacific area in 2007, and later in 2013-14. However, it was its arrival and dramatic spread in Brazil and other Latin American and Caribbean countries that alarmed public health authorities and the scientific community. Increasing evidence pointed to a link between the Zika virus and foetal microcephaly and Guillain-Barré syndrome, a rare condition in which the immune system attacks the nerves. This prompted the World Health Organisation (WHO) to declare ZIKV a Public Health Emergency of International Concern on 1 February 2016. In response to this emergency, research on ZIKV was intensified, and within a few months, large amounts of data and outstanding results have been produced.

Zika virus belongs to the genus Flavivirus, which includes other vector-borne viruses, like dengue virus and West Nile virus. Phylogenetic analysis has shown a close genetic similarity of ZIKV with dengue virus and has identified viral strains of the Asian lineage as responsible for the current epidemics. The virus is predominantly transmitted between humans through the bite of an infected mosquito, mostly of the species Aedes aegypti, but other modes of transmission have been identified, including trans-placental transmission between expectant mothers and their babies. Prolonged shedding of infectious virus in semen and in vaginal fluids and efficient viral replication in vaginal mucosa explain the ability of ZIKV to be transmitted sexually, a unique feature among flaviviruses. Recent experimental infection in mice also showed that the virus persistently infects peritubular cells and spermatogonia, induces inflammation in the testis and epididymis that leads to male infertility. Moreover, the virus was detected by immunohistochemistry in spermatozoa from a patient with acute infection.

Global Aedes aegypti mosquito (carriers of the Zika virus) distribution
Global Aedes aegypti distribution. CC0 1.0 via Wikimedia Commons.

Guillain-Barré syndrome was identified to be a very rare neurological complication, reported in about 1-3 out of 10,000 infections. The incidence of foetal demise, microcephaly, or other congenital anomalies is still unknown, and has been estimated to range from 1% to 20%, higher during the first trimester of pregnancy.

The structure of key ZIKV proteins has been characterized and could be exploited for the design of vaccines, therapeutic antibodies, and antiviral drugs. In vitro models and in vivo mouse and non-human primate models of ZIKV infection have been set up and used to investigate virus transmission, tropism, neural damage and teratogenicity, and to test the immunogenicity and efficacy of vaccines. These studies allowed us to clarify important mechanisms of ZIKV neuro-pathogenesis, such as the identification of neural progenitor cells and placental macrophages as targets for ZIKV infection in the human brain and in the placenta, and the demonstration that ZIKV efficiently counteracts the innate antiviral response in humans.

Similarly to other mosquito-borne viral infections, like West Nile fever and dengue fever, ZIKV disease is characterized by a mild fever, rash, and arthralgia, making it almost undistinguishable. Because of this, during the acute phase of infection, diagnosis must rely on molecular testing from blood, urine, or saliva, while serology testing may be inconclusive due to the cross-reactivity of antibodies with other flaviviruses. This represents a serious problem for the diagnosis of infection in people who reside in ZIKV endemic areas, where other flaviviruses, like dengue virus and yellow fever virus, generally co-circulate.

The strong genetic and structural similarities of ZIKV to other flaviviruses poses a challenge not only to the differential diagnosis, but also to vaccine development, because antibodies induced by a previous flavivirus infection or vaccination may worsen a subsequent infection with a heterologous flavivirus through a mechanism of antibody-mediated enhancement.

Nonetheless, some vaccines against ZIKV have been developed and are in the process of clinical trial evaluation. In addition, drug repositioning screenings have identified some molecules that inhibit ZIKV infection and replication, while genome-wide screenings have identified certain human genes that are essential for ZIKV to replicate in the body, which could hold answers for finding effective antiviral therapies.

Several questions still remain open, such as how the virus infects and interacts with mosquito and human cells; which are the key genetic and molecular determinants of pathogenesis; how long the virus persists in human blood and tissues and its transmissibility; and how the innate and adaptive immune responses can counteract the virus and protect from reinfection. The responses to these questions are crucial, in this New Year and the future, to developing new antiviral medicines and improved protocols for ZIKV control.

Featured image credit: Zika virus 3D by Manuel Almagro Rivas. CC BY-SA 4.0 via Wikimedia Commons.

Recent Comments

  1. Rose Webster

    False: “Phylogenetic analysis has shown a close genetic similarity of ZIKV with dengue virus.”

    Fact: There is 99 percent support for the phylogenetic placement of Zika within the clade that includes: West Nile Virus (WNV) and St. Louis Encephalitis Virus (SLEV).

    Dengue and Yellow Fever fall outside that clade (and are hemorrhagic diseases). Zika is clearly a neurological, reproductive, and sexually transmitted disease.

    False: “The virus is predominantly transmitted between humans through the bite of an infected mosquito, mostly of the species Aedes aegypti.”

    Fact: Many scientists (Drs. Ayres, Hunter, Leal, and others) believe the Culex genus is similarly (or primarily) responsible for the spread of Zika.

    We did know this: “how long the virus persists in human blood”.

    At least 2 months was the warning from a study conducted Dec 2015 – April 2016. Source: Eurosurveillance Rapid Communication Detection of Zika Virus RNA in Whole Blood of Imported Zika Virus Disease Cases Up to 2 Months After Symptom Onset, Israel, December 2015 to April 2016.

    More recent (Dec. 2016): “detection of Zika virus RNA in vaginal secretions up to day 14 and in erythrocytes up to day 81” (almost 3 months in blood). Source: December 14, 2016 CDC post called Prolonged Detection of Zika Virus in Vaginal Secretions and Whole Blood.

    The WHO ignored the early warnings in February 2016 about the Culex genus of mosquitoes and now Zika is spreading throughout the poorest regions of the globe.

    Our public health authorities failed to contain the virus and repeatedly downplayed or ignored crucial scientific facts.

    Culex mosquitoes in Brazil and China are spreading Zika (which means birds are likely reservoir hosts). What’s worse: Wolbachia that is acquired by any species after (or perhaps along with) a Zika infection is probably enhanced by Wolbachia.

    Source: http://www.infobarrel.com/More_Proof_Wolbachia-Infected_Mosquito_Releases_Might_Be_Causing_the_Most_Devastating_Zika_Infections

  2. Frankli David Nash, MD

    Please, readers, do not underestimate the subsequent consequences of ZIKV-induced Guillain-Barré syndrome (GBS).

    Although not as actively transmitted as was/is polio, I well remember polio’s post-paralytic complications and costs. In the early 1960s, I was a trauma surgery resident at a large university medical center. Whereas before the 1950s polio epidemic, trauma service admitted fractures one day a week so the residents could get that experience, during my active service, we handled fractures three days a week. Why? What did that have to do with polio?

    Simply said, there were so many post-polio patients needing surgery like tendon trasfers to improve their physical functions (e.g., walking) that the orthopedic surgery service did not have time to handle both corrective surgery for post-polio patients and fractures and multiple systen injuries.

    In most of the USA, the ZIKV is, relatively speaking, dorment now. But it will be in the news again come the warm weather and rains. So, we will see ZIKV-induced GBS cases requiring surgical correction as did so many of the post-polios. Their preparation, surgical care, and recovery, involving physical and occupational therapy (PT and OT), will be costly, not to menthion those who will not qualify, financially or surgically, who will need similar therapy.

    And so, as I write this, I have no idea what the Repubican Triumverate (Trump, House, and Senate) will produce in terms of national health care. Nevertheless, I hope at least one of those involved in the deliberations brings to the table the presumptive costs of the GBS itself and the orthopedic surgical costs as well as those of PT and OT.

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