Why secodary dengue infection more virulent?

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Discussion Overview

The discussion centers on the virulence of secondary dengue infections, particularly the mechanisms that lead to more severe outcomes when a person is infected with a different serotype after an initial infection. Participants explore the underlying pathology and compare it to other viral infections, such as HIV.

Discussion Character

  • Exploratory
  • Technical explanation
  • Debate/contested

Main Points Raised

  • One participant inquires about the exact pathology behind severe infections resulting from secondary dengue infections with different serotypes.
  • Another participant suggests that severe outcomes may be due to massive cytokine release, leading to complications such as disseminated intravascular coagulation (DIC).
  • It is proposed that while immunity to a specific dengue serotype is developed after the first infection, this immunity does not extend to other serotypes, potentially worsening subsequent infections.
  • A further explanation introduces the concept of antibody-mediated enhancement, where antibodies from the first infection bind to a different serotype but do not neutralize it, facilitating entry into cells.
  • One participant draws a parallel to HIV, discussing the potential for similar mechanisms of enhanced infection and the ongoing debate regarding vaccine effects.

Areas of Agreement / Disagreement

Participants express multiple competing views regarding the mechanisms behind the increased virulence of secondary dengue infections, particularly concerning cytokine release and antibody-mediated enhancement. The discussion remains unresolved with no consensus reached.

Contextual Notes

Limitations include the lack of detailed exploration into the specific immune responses involved in different serotypes and the potential variability in responses among different populations, such as monkeys compared to humans.

Who May Find This Useful

Researchers and students interested in virology, immunology, and the complexities of viral infections and their interactions with the immune system may find this discussion relevant.

sameeralord
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If u get infected with X serotype of dengue. And then you get infected again with Y serotype you get a severe infection. What is the exact pathology behind this. Also what happens if you get infected by X serotype again, do you get severe infection then as well. Thanks :smile:
 
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Its thought the reason that reinfection with other serotypes of dengue is so bad is due to more massive cytokine release on the part of the host (humans in this case, I'm not sure how the monkeys that get dengue react to reinfections). So the DIC and other complications are mediated by a cytokine-stormish scenario.

After infection from one dengue serotype, supposing you don't get hemorrhagic fever and die, you should have immunity to that specific serotype--however it does not confer immunity to other serotypes and as mentioned above makes subsequent infections worse.
 
Thanks bobze :smile:
 
To add to the last post, the reason why subsequent infections with different serotypes can be much worse is due to the phenomenon of antibody-mediated enhancement.

As was already said, infection with one serotype will result in the production of antibodies that neutralize that specific serotype. If the same person then becomes infected with a different serotype, those antibodies will then bind to, but not neutralize the new virus. This antibody "coat" on the new virus actually allows it to more easily enter and infect new cells by interacting with antibody Fc receptors.
 
I think that the same goes for HIV, right? The enhancement of infection of the MT 2T-cell, specifically. I think there is some debate going about the sub-neutralizing effects of the vaccine given to volunteers in a study which might lead to a better immune response to HIV. This page here lists many of the antibodies used for these studies. I find it very useful. I personally find it very interesting how companies do progress in this field, but there is still much to be done to develop an effective vaccine.
 

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