Zika virus (ZIKV) is a mosquito-borne flavivirus that was first isolated from a rhesus monkey in the Zika forest of Uganda in 1947. In 1968, isolation from human hosts occurred in residents of Nigeria. Since then, multiple studies have confirmed ZIKV antibody in humans from a multitude of countries in Africa and parts of Asia.
In 2015, ZIKV first appeared outside of Africa and Asia when it was isolated in Brazil where is has caused a minor outbreak following the 2014 FIFA World Cup. ZIKV is closely related to other mosquito-borne flaviviruses such as the dengue, yellow fever, West Nile, and Japanese encephalitis viruses. ZIKV causes a disease known as Zika fever, which is characterized by a macropapular rash covering the body, fever, joint pain, and malaise. Although there have yet to be serious complications arising from ZIKV, it's appearance across the globe, mosquito-driven transmission cycle, and possible spread via sexual contact make ZIKV an important emerging pathogen whose global impact is yet to be discovered.
Genome Structure
The Zika virus is a positive sense single-stranded RNA molecule 10794 bases long with two non-coding regions flanking regions known as the 5' NCR and the 3' NCR. The open reading frame of the Zika virus reads as follows: 5′-C-prM-E-NS1-NS2A-NS2B-NS3-NS4A-NS4B-NS5-3′ and codes for a polyprotein that is subsequently cleaved into capsid (C), precursor membrane (prM), envelope (E), and non-structural proteins (NS). The E protein composes the majority of the virion surface and is involved with aspects of replication such as host cell binding and membrane fusion. NS1, NS3, and NS5 are large, highly-conserved proteins while the NS2A, NS2B, NS4A, and NS4B proteins are smaller, hydrophobic proteins. Located in the 3' NCR are 428 nucleotides that may play a part in translation, RNA packaging, cyclization, genome stabilization, and recognition. The 3' NCR forms a loop structure and the 5' NCR allows translation via a methylated nucleotide cap or a genome-linked protein.
Virion Structure of a Zika virus
The structure of ZIKV follows that of other flaviviruses. It contains a nucleocapsid approximately 25-30 nm in diameter surrounded by a host-membrane derived lipid bilayer that contains envelope proteins E and M. The virion is approximately 40 nm in diameter with surface projections that measure roughly 5-10 nm. The surface proteins are arranged in an icosohedral-like symmetry.Viral Ecology & Pathology
Epidemiology
Since it's first detection in Uganda, ZIKV has appeared in the following countries of Africa and Asia: Gabon, Egypt, Nigeria, Senegal, Sierra Leone, Côte d'Ivoire, Central African Republic, Cambodia, Micronesia, Malaysia, Pakistan, India, Thailand, Philippines, and Indonesia. ZIKV has also presented itself in the Western world in 2015 when it was isolated in Brazil, likely a result of the 2014 World Cup.
Transmission
The transmission of ZIKV is predominately through the use of mosquitoes as vectors. However, a recent case shows that human-to-human contact is possible, which would make it the first time an insect-borne disease was passed via sexual contact. In nature, reservoirs for ZIKV virus are restricted to primates. However, one study showed antibody to ZIKV in rodents. Due to the oddity of transmission through sexual contact, further studies should be conducted to identify all possible reservoirs and insect vectors to further understand ZIKV transmission.Mosquito-borne
Transmission of ZIKV in nature is thought to follow that of other closely related flaviviruses. This transmission includes a mosquito vector and a mammalian host. For ZIKV, a variety of mosquitoes from the genus Aedes are viable vectors.These include A. africanus, A. aegypti, A. vitattus, A. furcifer, A. apicoargenteus, and A. luteocephalus. Horizontal transmission is the terminology given to transmission of viruses from mosquito vectors to mammalian hosts. On the contrary, vertical transmission is the result of mosquito populations passing on the virus to their offspring. Transmission occurs when an infected vector feeds on a host. Studies show that the incubation time for ZIKV in mosquito vectors is approximately 10 days.
Human to Human
After returning from a research mission to Senegal, Dr. Brian Foy of the University of Colorado appeared to have passed ZIKV to his wife after sexual intercourse in 2008. Both Dr. Foy and his Ph.D. student Kevin Kobylinski were bitten by numerous mosquitoes while abroad and became ill about 5 days after returning to the U.S. Both showed signs of Zika fever and Dr. Foy's wife saw what she believed to be blood in his semen. Approximately 10 days later, Foy's wife showed signs of Zika fever while their four children remained healthy. At first it was believed that Foy had contracted dengue fever, but after Kobylinski had an encounter with medical entomologist Andrew Haddow who had experience with ZIKV, tests were run that confirmed all three patients possessed antibody for ZIKV. Circumstantial evidence suggests that sexual contact was the mode of transmission due to the high unlikeliness that Foy's wife was bitten by the tropical Aedes mosquito in Colorado. Additionally, the virus requires a 2-week life cycle in mosquito hosts before infecting humans and Foy's wife showed symptoms merely 10 days upon his return.
Zika Fever and ZIKV Pathogenesis
Zika fever is the disease associated with ZIKV infection. While there are scarce resources describing ZIKV pathogenesis exclusively, the general consensus is that mosquito-borne flaviviruses replicate initially in the dendritic cells at the site of infection where it then spreads to other areas of the body via the bloodstream and lymphatic system. Viral replication typically occurs in the cytoplasm of infected cells, but there is a study that shows ZIKV antigens can also be found in the nuclei of infected host cells.
Symptoms
The first well-documented case of Zika fever in 1964 describes symptoms as beginning with a headache and then continuing to include a maculopapular rash covering a significant portion of the body the following day. In addition, a fever was present as well as back pain and a general feeling of malaise. In 1973, a patient with Zika fever presented with fever, joint pain, and headache but the rash was absent. Another outbreak in Indonesia resulted in all 7 victims showing fever, but varying additional symptoms ranging from abdominal pain and dizziness to diarrhea and anorexia but no signs of rash. The outbreak on Yap Island showed the maculopapular rash, joint pain, and conjunctivitis. In all cases, symptoms were mild and typically self-resolved in the course of a week without the need for hospitalization or risk of severe complications.
Diagnosis
Diagnosis for ZIKV infection include PCR tests to detect viral DNA as well as additional tests to detect ZIKV antibody (IgM) in serum. IgM for ZIKV is typically detectable around 3-5 days after infection, but cross-reactivity with closely related dengue, yellow fever, Japanese encephalitis, and West Nile viruses are possible. These cross-reactive results were more common in patients that denoted signs of previous flavivirus infection than patients with primary ZIKV infection. PCR tests should be conducted within 10 days of onset of illness. For best diagnosis practices, serum samples should be analyzed as early as possible with a second test 2 to 3 weeks after that.
Treatment and Prevention
Presently, there is no vaccine for ZIKV or treatment for Zika fever. Because symptoms are relatively mild and the disease is self-limiting, only supportive therapy is employed. Patients with Zika fever should remain hydrated and rest. Acetaminophen can be prescribed to combat fever.
Given that ZIKV is transmitted by mosquitoes, it is advocated by the CDC to use insect repellent, long sleeved-clothing, and intervention in reducing the number of mosquito vectors. Additionally, due to recent studies that show the possibility of sexual transmission, safe sex practices are also encouraged.
Information from Microbewiki
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