Dengue Virus Antibodies Enhance Zika Virus Infection

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Q&A with Scott Halstead: Zika will subside in ‘5 years, max’

Q&A with Scott Halstead: Zika will subside in ‘5 years, max’

By Jon CohenMar. 7, 2016 , 11:00 AM

snips


Q: Do you think an antibody enhancementlike feature with Zika is behind the severe disease that’s been linked to microcephaly in babies and Guillain-Barr? syndrome in adults?

A: Absolutely. I’m certain of it. I’d bet a lot of money.

In the 1980s Ademola Fagbami from Nigeria came to my lab at the University of Hawaii with Zika virus and we did an experiment, which we published, that showed it can be enhanced in mononuclear phagocytes [a type of immune cell]. We know that it grows in those cells and that antibody can enhance it. Zika is actually genetically fairly close to the dengue viruses, which means a lot of surface proteins on Zika are identical to surface proteins on dengue. It absolutely would not surprise me to find that dengue antibodies enhance Zika infections and that this entire sweep of Zika across the Pacific and into South America has all been promoted and propelled by enhancement.

Q: What are the main unknowns about Zika?

A: Does it grow in primary human monocytes in vitro? If somebody dies can we find the virus in monocytes and macrophages in vivo? Those are the key things.

Q: What might be the mechanism behind Zika virus harming fetuses?

A: I think dengue antibody is complexing with Zika virus and the immune complex is infecting monocytes so you have a much higher amount of virus produced. Maybe above a certain concentration of virus you begin to get virus spilling over into placenta.
...

http://www.sciencemag.org/news/2016/...de-5-years-max

 

[sharon sanders]

Dengue Virus Antibodies Enhance Zika Virus Infection

Lauren M Paul, Eric R Carlin, Meagan M Jenkins, Amanda L Tan, Carolyn M Barcellona, Cindo O Nicholson,Lydie Trautmann, Scott F Michael, Sharon Isern
doi: http://dx.doi.org/10.1101/050112

snip

We show that anti-DENV HMAbs, cross-react, do not neutralize, and greatly enhance ZIKV infection in vitro. DENV immune sera had varying degrees of neutralization against ZIKV and similarly enhanced ZIKV infection.

Conclusions / Significance
Our results suggest that pre-existing DENV immunity will enhance ZIKV infection in vivo and may increase disease severity. A clear understanding of the interplay between ZIKV and DENV will be critical in informing public health responses in regions where these viruses co-circulate and will be particularly valuable for ZIKV and DENV vaccine design and implementation strategies.

http://biorxiv.org/content/early/2016/04/25/050112


hat tip @greg_folkers

 

[sharon sanders]

The April 1 PAHO report shows that Brazil is reporting 495,266 probable dengue infections to date for 2016. link This infection number is the largest number of reported cases for the Americas and may be an under count. Please see the EID letter:

"We showed that dengue surveillance substantially underestimated disease burden in Brazil, especially in what are considered low-transmission periods. Dengue underreporting has been attributed to passive case detection, which fails to identify persons with dengue who do not seek health care (1). We also showed that surveillance failed to detect dengue cases among symptomatic patients seeking health care." link

 

[sharon sanders]

[h=2]Tuesday, April 26, 2016[/h] [h=3]Dengue & Zika: Does What Goes Around, Come Around?[/h]

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#11,312


More than two years ago, in Zika, Dengue & Unusual Rates Of Guillain Barre Syndrome In French Polynesia,we looked at the first reports of serious illness linked to the Zika virus, and speculation that it might be due to concurrent or prior infection with Dengue.

A few weeks later, in a Eurosurveillance report (see Zika Virus Infection Complicated By Guillain-Barr? Syndrome), the authors wrote:

Our patient, like part of others who also presented a GBS, harboured serological markers of resolute dengue and recent ZIKA infections. This raises the hypothesis of a sequential arboviral immune stimulation responsible for such unusual clustering of GBS cases during concurrent circulation of ZIKA and two dengue serotypes. The risk of developing GBS would be consequently underlain by a specific sequence of DENV and ZIKA infections.​

It is not so far-fetched an idea, as we see it sometimes in sequential dengue infections, in a phenomenon called ADE (Antibody Dependent Enhancement).

There are 4 distinct, but closely related, serotypes of the Dengue virus, and the first infection of any serotype is usually mild. The patient recovers with lifetime immunity, but remains susceptible to the other three serotypes.​

When infected a second time,the host?s immune system - which already has neutralizing antibodies against the first DENV infection - misidentifies the second DENV infection as the first strain.

Rather than creating new neutralizing antibodies to fight the infection, it deploys its existing cross reactive, but non-neutralizing (read:ineffective) antibodies to the field of battle.​

When congenital birth defects began cropping up in Brazil last fall, the ADE theory was immediately suggested as a possible contributing factor, since Zika is genetically very similar to Dengue.

You'll find a January discussion here, and in February Helen Branswellwrote Dengue could be the surprise culprit making Zika worse, researchers say.

While this is all still an unproven theory, if true, it offers hope that the risks of seeing severe fetal outcomes, or neuroinvasive disease, are less in regions where other flaviviruses are not endemic.​

Adding a bit more fuel to this hypothesis, we have a new paper - that whilenot yet published in a peer-reviewed journal - has been offered as a preview on the BioRxiv (Bio Archive)site, called:

Dengue Virus Antibodies Enhance Zika Virus Infection,m

Lauren M Paul, Eric R Carlin, Meagan M Jenkins, Amanda LTan, Carolyn M Barcellona, Cindo O Nicholson, LydieTrautmann, Scott F Michael, Sharon Isern
doi: http://dx.doi.org/10.1101/050112


[h=2]Abstract[/h] Background For decades, human infections with Zika virus (ZIKV), a mosquito-transmitted flavivirus, were sporadic, associated with mild disease, and went underreported since symptoms were similar to other acute febrile diseases endemic in the same regions. Recent reports of severe disease associated with ZIKV, including Guillain-Barre syndrome and severe fetal abnormalities, have greatly heightened awareness. Given its recent history of rapid spread in immune naive populations, it is anticipated that ZIKV will continue to spread in the Americas and globally in regions where competent Aedes mosquito vectors are found.

Globally, dengue virus (DENV) is the most common mosquito-transmitted human flavivirus and is both well-established and the source of outbreaks in areas of recent ZIKV introduction. DENV and ZIKV are closely related, resulting in substantial antigenic overlap. Through a mechanism known as antibody-dependent enhancement (ADE), anti-DENV antibodies can enhance the infectivity of DENV for certain classes of immune cells, causing increased viral production that correlates with severe disease outcomes.

Similarly, ZIKV has been shown to undergo ADE in response to antibodies generated by other flaviviruses. However, response to DENV antibodies has not yet been investigated.

Methodology / Principal Findings We tested the neutralizing and enhancing potential of well-characterized broadly neutralizing human anti-DENV monoclonal antibodies (HMAbs) and human DENV immune sera against ZIKV using neutralization and ADE assays. We show that anti-DENV HMAbs, cross-react, do not neutralize, and greatly enhance ZIKV infection in vitro. DENV immune sera had varying degrees of neutralization against ZIKV and similarly enhanced ZIKV infection.

Conclusions / Significance Our results suggest that pre-existing DENV immunity will enhance ZIKV infection in vivo and may increase disease severity. A clear understanding of the interplay between ZIKV and DENV will be critical in informing public health responses in regions where these viruses co-circulate and will be particularly valuable for ZIKV and DENV vaccine design and implementation strategies.

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Follow the above link to read the full PDF of the study.




Posted by Michael Coston at 10:28 AM