Dengue virus infection-an interesting immunological explanation why you do not want to get it.
Dengue fever is a mosquito-borne (Aedes aegypti) tropical disease that is caused by any of the four serotypes of the Dengue virus (DV). (A “serotype” is a specific microorganism as characterized by serologic typing-aka, testing for recognizable antigens on the surface of the microorganism.)
There are an estimated 50-100 million cases of Dengue fever (DF) per annum worldwide, 500000 of which result in the severe form of the disease, Dengue hemorrhagic fever (DHF) marked by abnormal vascular permeability.
Humans, mosquitos and some primates can be infected through the bite of infected A. aegypti that breed in domestic and peridomestic water containers.
DV causes an acute infection that is effectively controlled after 3 to 7 days. Individuals that have recovered from DV infection are immune to re-challenge with the same type but not with other serotypes of DV. Sequential infection with a second serotype usually results in the severe form of disease, DHF. In short, this virus can and will cause a very painful death in most people who get infected again, but this time with a different serotype.
If you think about this, the question that arises is the following:
What makes the secondary infection with the virus much worse than the first?
Interestingly, this phenomenon has little to do with the direct activation of immune cells through antigen expressed by the infecting virus.
Studies have lead to the hypothesis that infection with a second dengue virus serotype results in antibody-mediated immune enhancement. Antibodies generated against the first infecting serotype (#1) will bind the second (#2). Unfortunately, these antibodies are not able to neutralize serotype #2 and they will facilitate FC-receptor mediated and complement-mediated virus-uptake and replication in phagocytic cells (ADE-antibody-dependent enhancement). This means that the same antibody that works well to decrease the number of the first infecting virus does the exact opposite to the second infecting virus. By helping it to enter phagocytic cells it helps more viral particles to grow and more viral offspring will infect new cells. In the end, the virus will take over and the patient’s immune system will not be able to fight it anymore.
This increased severity of a secondary infection has been observed in different virus infections in vitro (aka, in a test tube) and one can imagine that it could potentially be a problem when new vaccines are created. For example, imagine giving a vaccine against serotype 1 of the HIV virus and the person is getting infected with serotype 2. This means that the person’s immune system has already created antibodies against serotype 1 (this is the whole idea behind vaccinations) that –unfortunately- can help to enhance viral entry of serotype 2 into the host cell. As a result, the infectivity of serotype 2 increases.
Selected references
Dengue fever is a mosquito-borne (Aedes aegypti) tropical disease that is caused by any of the four serotypes of the Dengue virus (DV). (A “serotype” is a specific microorganism as characterized by serologic typing-aka, testing for recognizable antigens on the surface of the microorganism.)
There are an estimated 50-100 million cases of Dengue fever (DF) per annum worldwide, 500000 of which result in the severe form of the disease, Dengue hemorrhagic fever (DHF) marked by abnormal vascular permeability.
Humans, mosquitos and some primates can be infected through the bite of infected A. aegypti that breed in domestic and peridomestic water containers.
DV causes an acute infection that is effectively controlled after 3 to 7 days. Individuals that have recovered from DV infection are immune to re-challenge with the same type but not with other serotypes of DV. Sequential infection with a second serotype usually results in the severe form of disease, DHF. In short, this virus can and will cause a very painful death in most people who get infected again, but this time with a different serotype.
If you think about this, the question that arises is the following:
What makes the secondary infection with the virus much worse than the first?
Interestingly, this phenomenon has little to do with the direct activation of immune cells through antigen expressed by the infecting virus.
Studies have lead to the hypothesis that infection with a second dengue virus serotype results in antibody-mediated immune enhancement. Antibodies generated against the first infecting serotype (#1) will bind the second (#2). Unfortunately, these antibodies are not able to neutralize serotype #2 and they will facilitate FC-receptor mediated and complement-mediated virus-uptake and replication in phagocytic cells (ADE-antibody-dependent enhancement). This means that the same antibody that works well to decrease the number of the first infecting virus does the exact opposite to the second infecting virus. By helping it to enter phagocytic cells it helps more viral particles to grow and more viral offspring will infect new cells. In the end, the virus will take over and the patient’s immune system will not be able to fight it anymore.
This increased severity of a secondary infection has been observed in different virus infections in vitro (aka, in a test tube) and one can imagine that it could potentially be a problem when new vaccines are created. For example, imagine giving a vaccine against serotype 1 of the HIV virus and the person is getting infected with serotype 2. This means that the person’s immune system has already created antibodies against serotype 1 (this is the whole idea behind vaccinations) that –unfortunately- can help to enhance viral entry of serotype 2 into the host cell. As a result, the infectivity of serotype 2 increases.
Selected references
- Tirado SM, Yoon KJ. 2003. Antibody-dependent enhancement of virus infection and disease. Viral Immunol 13(6): 387
- Takada A, Kawaoka Y. 2003. Antibody-dependent enhancement of viral infection: molecular mechanisms and in vivo implications. Rev Med Virol 16(1): 69
6 comments:
This is fascinating stuff!! Just an FYI, on the Science channel (cable) there's a great show called "Understanding" and tomorrow morning (at least in AZ) they are doing viruses! I caught a little today and they discuss dengue fever in detail!!
That sounds very interesting.....but I don't have cable......do you know whether they podcast this show?
I'm not sure...there's not much information on the Science Channel website...I may send them an email and see what I find out!!
Sandra, how interesting! In the public health literature, dengue fever is always a catch-phrase. Out of curiousity, I just checked the Colorado Department of Health and Environment health surveillance reportable condition statistics (www.cdphe.state.co.us). It turns out the last reported cases of dengue fever in Colorado were in 2001 (4 cases) and 2002 (5 cases, 3 from my county of Araphaoe!) I wonder...I'm thinking back. I belive 2002 or possibly 2003 was when the West Nile virus scare was beginning...I wonder if the reduction in incidence of dengue fever has to do with better control of the mosquitoe population? What a great article you've written...very informative. Even dengue fever seems possible in Colorado, so it's good (and scary) information you've given us. TLH
Dengue is spreading world-wide; as terih7630 says, it's even been seen in Colorado (AZ folks: is it even more common in your hotter state, or is it too dry for skeeters?)
Did you know the connection between dengue and cars? Tires are indestructible: you can't burn them and they never decompose. Also, no matter what position a tire is in when it's thrown away, it will catch and retain rain water. Result: instant mosquito breeding incubator.
It is too dry in most parts of Arizona. I lived in Phoenix for 5 years and didn't see a single mosquito. I had no idea that we had dengue in Colorado.
Side Note - Is the spreading due to the global warning people say doesn't exist? Does Al Gore know about this?
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