Two children with rare genetic mutation resistant to influenza, herpes, hep C, HIV

Glycosylation, Hypogammaglobulinemia, and Resistance to Viral Infections

Source

This has been making the rounds in various media sites, but I didn't see a thread pop up so hopefully it's new to the forum.



Two kids with a genetic mutation were found to have increased viral resistance, sadly, their mutations also caused neurological complications. So while this abnormality is probably not sought after in itself, there may be some underlying actions by their body function that can be exploited in the future.

Genetic defects in MOGS, the gene encoding mannosyl-oligosaccharide glucosidase (the first enzyme in the processing pathway of N-linked oligosaccharide), cause the rare congenital disorder of glycosylation type IIb (CDG-IIb), also known as MOGS-CDG. MOGS is expressed in the endoplasmic reticulum and is involved in the trimming of N-glycans. We evaluated two siblings with CDG-IIb who presented with multiple neurologic complications and a paradoxical immunologic phenotype characterized by severe hypogammaglobulinemia but limited clinical evidence of an infectious diathesis. A shortened immunoglobulin half-life was determined to be the mechanism underlying the hypogammaglobulinemia. Impaired viral replication and cellular entry may explain a decreased susceptibility to infections.

How's it work exactly?

Most proteins, including immunoglobulins, human virus receptors, and viral-coded proteins, are post-translationally modified with sugars or sugar chains that are generically referred to as glycans. Glycans are primarily classified as N-linked or O-linked oligosaccharides, depending on whether they are bound to the amide group of asparagine (N-linked) or the hydroxyl group of serine or threonine (O-linked). Glycans are associated with protein conformation, folding, solubility, stability, half-life, and antigenicity and are the moieties recognized by glycan-binding proteins. The congenital disorders of glycosylation (CDGs) are genetic disorders affecting the N-glycosylation process. CDGs are divided into defects in the synthesis of N-glycans (CDG-I) and defects in the processing of N-glycans (CDG-II). CDG-IIb (Online Mendelian Inheritance in Man database number, 606056) is caused by mutations in the gene encoding MOGS (also known as glucosidase 1). MOGS is an enzyme that is expressed in the endoplasmic reticulum and is involved in the trimming of N-glycans.1 A single case of CDG-IIb has been reported; the patient died at the age of 74 days from severe neurologic complications.2 In this study, we evaluated the immune system and susceptibility to viral diseases in two siblings with CDG-IIb who presented with severe hypogammaglobulinemia but not many infections.

Future prospects?

Furthermore, as suggested by the effects of castanospermine on viral glycoproteins (Figure 2B), there is a strong potential benefit of using inhibitors of MOGS as a means of controlling viral infections, especially those that pose a threat of rapid global spreading. Previous in vitro studies have shown that MOGS inhibitors such as castanospermine, N-butyldeoxynojirimycin (miglustat; previously known as NB-DNJ), or deoxynojirimycin can reduce viral replication in HIV infection, dengue, herpes simplex virus type 2 infection, and hepatitis C.

Interesting to say the least. Seems like there is a surge in the medical and research community in regards to understanding viral and genetic functions. Sophiecrow (?) always has some decent threads on this kind of thing, which I recommend looking up ATS threads by that author if this kind of thing interests you.

The price of immunity?

Early in life, they each had a complex disorder characterized by dysmorphic facial features, generalized hypotonia, seizures, global developmental delay, cerebral atrophy, a small corpus callosum, optic-nerve atrophy, sensorineural hearing loss, hypoplastic genitalia, chronic constipation, and recurrent bone fractures; severe hypogammaglobulinemia was also diagnosed. The patients were evaluated for the frequency of febrile episodes

Interesting find OP, a male and female, strange I will be all crazy and call them Adam and Eve of the post apocalypse , except they are brothers and that is just creepy

reply to post by Indigent


Yeah, it's pretty terrible the quality of life and the complications they suffered. Perhaps if they can take the information gathered from studying them, they can develop new treatments inspired by the mutations, which might make up for the suffering they endured. Maybe not to them, but to the people who could benefit from it.

There are some foods, spices, and Herbs out there that can reduce viral replication. They all seem to have problems if either eaten too often or are eaten at the wrong time. The meds that reduce viral replication have side effects if used too much, the thing about this is that they also keep certain types of our cells from replicating most times. They are getting better at making them target just viruses but are far from accomplishing this correctly. I think Tamaflu may block replication. I think the reason pine needle tea, which contains the chemical in tamaflu, is bad for pregnant women is because it blocks cell replication.

reply to post by boncho


F&S& Important - and as Indigent says, "The price of immunity." ...I suspect we'll be seeing a lot more of this stuff assuming we don't jump straight into Eugenics-euthanasia to take care of the wrong problems in the wrong way.

Perhaps we are seeing some of the early steps of evolution in the works here. This could be an evolutionary step towards humans becoming resistant to these diseases that are meant to wipe us out. Granted the other complications are awful, but mutation and evolution do not happen overnight.....

reply to post by Vasa Croe

This could be an evolutionary step towards humans becoming resistant to these diseases that are meant to wipe us out. Granted the other complications are awful, but mutation and evolution do not happen overnight.....

Seems to me most diseases are evolutionary steps, glitchy til the smooth assimilation.

Interesting, particularly if there really is a neurological connection.

However, I wonder how "rare" this really is, seeing as many people may be resistant to these things but don't necessarily get tested.

a reply to: Vasa Croe

Let's examine this...
In order for this to be an evolutionary step, it must be passed on to the next generation and provide a survival advantage, or at worst, not be a survival disadvantage.

The side effects of this mutation sound pretty debilitating, so what would it take in order to make the tradeoff worth it, from an evolutionary perspective?

A highly virulent strain of some virus that they have immunity to would have to sweep the population, leaving them living, along with any others who share their resistance.
Then they would have to reproduce and pass on this mutation to their children, who would also have to survive not only the disease, but the side effects of their mutation, and so on and so forth.
It seems to me that a less drastic mutation that provided less viral resistance, but also less damage to the brain, eyes, etc... would be more beneficial, evolutionarily speaking.