ABO Polymorphism & Disease Susceptibility
Infectious Diseases (2)
In addition to the binding of infectious agents to ABH antigens on host cells, another type of interaction also exists between ABH antigens on viruses and naturally occurring antibodies against A/B antigens. ABH antigens may be added to the viral proteins while they are synthesized in the cells producing those antigens. The glycolipids of membrane-encapsulated viruses may also possess ABH antigens from the cells. Because those viruses may exhibit ABO polymorphism and the new host may contain antibodies against A/B antigens in sera, the host ABO phenotype is likely to affect the susceptibility towards those viruses.
The first demonstration of such interaction came with the α1,3Gal epitope and the antibody against that oligosaccharide structure. Retrovirus produced in mouse cells express the α1,3Gal epitope. The GGTA1 gene which encodes the α1,3Gal transferase, an enzyme evolutionarily related with A and B transferases, is non-functional and has become a pseudogene in Homo sapiens. Therefore, humans cannot synthesize the α1,3Gal epitope. Instead, humans possess antibodies against this structure. The anti-α1,3Gal epitope antibody in human sera could inactivate the retroviruses produced by murine cells. Apparently, this seems to be one of the molecular mechanisms that inhibit the inter-species infection of the retroviruses from mouse to human. It should be noted that once infection is established, the viruses take the phenotype of the new host, and the inhibition will no longer be effective.
We thought of a similar scheme with the ABO phenotype of the host. Collaborating with Dr. Hirokazu Inoue, we produced xenotropic retroviruses from HeLa cells exhibiting different ABO phenotypes (The ABO phenotype of the original cells was O. We transfected expression constructs encoding for human A and B transferase and produced HeLa cells with A and B phenotypes). Those viruses were mixed with sera from individuals with different ABO blood types, and the changes in infectivity were monitored. We anticipated selective inhibition; however, the results showed that most viruses were inactivated by the sera irrespectively of the ABO phenotype of the virus-producing host cells and of the sera. Although we failed to show the inhibition of the intra-species infection of retroviruses, other groups were successful. Using the model systems of measles viruses and HIVs, the ABO mediated selective inhibition was demonstrated.
It is possible that the differential susceptibility to such selective forces as infectious agents may have resulted in the observed geographical and racial differences in ABO-phenotypes frequency.
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