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flaviviruses

So I read this article on NPR, so I thought I could write what I know pertaining to the subject. The article discusses the arbovirus (arthropod-borne virus) such as dengue virus (DENV) and Zika virus (ZIKV). The article mentioned some other arboviruses detected in athletes and staffs’ sera, e.g. West Nile virus (WNV) and chikungunya virus (CHIKV). With an exception to CHIKV, all three of the aforementioned viruses are of the same family: the Flaviviridae.

It might not be obvious at first but here’s the challenge with Flaviviridae: antibodies against them seem to cross-react. What’s the implication? It could render some tests to yield false-positive results. For example, a person with a history of the previous infection of ZIKV might show up positive on DENV’s serological test. This is unfavorable to get an accurate history of a previous flavivirus infection, but it has some good thing about it.

Let’s talk about the good thing first.

First, as far as my knowledge goes, currently available and licensed vaccines against flaviviruses are for tick-borne encephalitis virus (TBEV), Japanese encephalitis virus (JEV), and yellow fever virus (YFV). The vaccine against DENV is still being extensively studied as of now (CYD-TDV a.k.a Dengvaxia). According to a paper by Mansfield (2011), it seems that individuals vaccinated against TBEV, JEV, and YFV have a varying degree of protection against WNV infection. However, it is hard to say for sure because the protection is subjected to individuals (ugh).

Now, what’s the bad thing?

In the face of an outbreak, antibody cross-reactivity makes it harder to diagnose what’s the actual causative infectious agent, although the technology that we have nowadays seem to circumvent this problem already. In the good old days, RT-PCR (reverse-transcription) was performed to identify the viral causative agent, followed by antibody typing.

As for antibody typing, there are several ways to do it: enzyme immunoassay (e.g. ELISA) or challenge with virus isolated from patients with known antibodies. Since I don’t have an intimate familiarity with both methods, I won’t discuss them here. There is also a serological quantitative method to identify the virus, namely the plaque reduction neutralization assay (PRNT). Briefly, serum containing antibody obtained from patients is tested against known virus stock in a cell culture. This method is designated as a gold standard for quantitative measurement, but it suffers from one significant drawback: it takes days to actually observe the formation of plaque.

In identifying and assessing the infection, it is usually sufficient to analyze the viral glycoprotein of the flavivirus because it is the main antigen that invokes immunity. To some extent, the NS1 and prM proteins are also used as the means of identification.

I hope at some point I can learn how to perform the PRNT assay. It seems like a good technique to learn.

  • (Mansfield et al., Dec 2011), Flavivirus-induced antibody cross-reactivity. DOI: 10.1099/vir.0.031641-0
  • (Thomas et al., Nov 2009) Dengue Plaque Reduction Neutralization Test (PRNT) in Primary and Secondary Dengue Virus Infections