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Jauna ģenētiska mutācija un brīnumaina rω-1 olbaltumviela no tārpiem
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10.09.2019

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Reta ģenētiska mutācija, kas izraisa ekstremitāšu muskuļu distrofiju, aizsargā no HIV, pavēstījuši spāņu zinātnieki.
Jauni sasniegumi mutāciju atklāšanā, kas būtu potenciāli noderīgas cīņā ar HIV, parādījās tikai 10 gadus pēc tam, kad slavenais “Berlīnes pacients” izārstējās no HIV pēc donora, kuram bija gēna CCR5 mutācija, kaulu smadzeņu transplantācijas.
Spāņu zinātnieku atklātā mutācija attiecas uz gēnu TNPO3 un ir sastopama daudz retāk. To pirms dažiem gadiem konstatēja kādas spāņu ģimenes locekļiem, kas cieta no ekstremitāšu muskuļu 1. tipa distrofijas.
Ārsti, izmeklējuši ģimeni, noskaidroja, ka šis gēns varētu interesēt HIV pētniekus, jo tam ir noteikta loma vīrusa pārnešanā šūnu iekšienē. (Lasiet zemāk oriģinālrakstu angļu valodā.)
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Antigēni, kurus satur šistosomu olas, maina imūnsistēmas darbību, traucējot tās šūnām saistīties ar HIV daļiņām. Turklāt stimulē T-šūnu augšanu, kas ir daudz noturīgākas pret cilvēka imūndeficīta vīrusu. Pētījums publicēts žurnālā PLoS Pathogens.
Šistosomas ir parazītiskie plakani tārpi, kas dzīvo asinīs un dēj olas cilvēka vēnās. Šistosomu olas spēj cīnīties ar cilvēka imūnsistēmu, izdalot vielas, kas maina imūno atbildi. Galvenais mērķis, pret ko darbojas šistosomu olu vielas, ir dendrītu šūnas. Vielas, ko izdala parazīti (rekombinanta olbaltumviela rω-1), saistās ar dendrīta šūnu receptoriem, traucējot tiem normāli strādāt.
Dendrītu šūnas imūnsistēmai vajadzīgas tāpēc, lai T-šūnas (T-limfocītus) iepazīstinātu ar iekļuvušās infekcijas antigēniem. Pēc tam, kad dendrītu šūnas atnesušas limfmezglos antigēnus, aktivizējas dažādu tipu T-šūnas, kas iznīcina organisma apdraudējumu – patstāvīgi vai aktivizējot B-šūnas.
Parazīta aizsardzība darbojas tikai pret to HIV veidu, kas izmanto CCR5 receptors, lai iekļūtu šūnā. HIV, kas izmanto CXCR4, neizjūt nekādu traucējumu. Turklāt pētījums tika veikts tikai ar HIV-1, bet ne HIV-2. (Lasiet zemāk oriģinālrakstu angļu valodā.)
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Source: MedicaExpress | «Researchers identify second gene mutation linked to HIV resistance» | https://medicalxpress.com/news/2019-08-mutation-rare-muscle-disease-hiv-.html | 
<... A rare genetic mutation that causes a form of muscular dystrophy affecting the limbs also protects against HIV infection. 
The breakthrough comes a decade after American Timothy Brown, known as the "Berlin Patient," became the first person cured of HIV after a bone marrow transplant from a donor with a mutation of the CCR5 gene.
The newly-discovered mutation concerns the Transportin 3 gene (TNPO3) and is far more rare.
It was identified several years ago among members of a family in Spain who were suffering from type 1F limb-girdle muscular dystrophy.
Doctors studying the family learned that HIV researchers were interested in the same gene because it plays a role in transporting the virus inside cells.
They then got in touch with geneticists in Madrid, who took blood samples from those family members and infected the blood with HIV—revealing a welcome surprise.
The lymphocytes—white blood cells that are an important part of the immune system—of people with the rare muscular illness were naturally resistant to HIV, it emerged.
"This helps us to understand much better the transport of the virus in the cell," Jose Alcami, a virologist at the Carlos III Health Institute and co-author of a paper published in US journal PLOS Pathogens on the subject, told AFP. ...>
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Source: PLOS Pathogens | «Schistosoma mansoni soluble egg antigen (SEA) and recombinant Omega-1 modulate induced CD4+ T-lymphocyte responses and HIV-1 infection in vitro» | https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007924 |
<... Abstract
Parasitic helminths evade, skew and dampen human immune responses through numerous mechanisms. Such effects will likely have consequences for HIV-1 transmission and disease progression. Here we analyzed the effects that soluble egg antigen (SEA) from Schistosoma mansoni had on modulating HIV-1 infection and cytokine/chemokine production in vitro. We determined that SEA, specifically through kappa-5, can potently bind to DC-SIGN and thereby blocks DC-SIGN mediated HIV-1 trans-infection (p<0.05) whilst not interfering with cis-infection. DCs exposed to SEA whilst maturing under Th2 promoting conditions, will upon co-culture with naïve T-cells induce a T-cell population that was less susceptible to HIV-1 R5 infection (p<0.05) compared to DCs unexposed to SEA, whereas HIV-1 X4 virus infection was unaffected. This was not observed for DCs exposed to SEA while maturing under Th1 or Th1/Th2 (Tmix) promoting conditions. All T-cell populations induced by SEA exposed DCs demonstrate a reduced capacity to produce IFN-γ and MIP-1β. The infection profile of T-cells infected with HIV-1 R5 was not associated with down-modulation of CCR5 cell surface expression. We further show that DCs maturing under Tmix conditions exposed to plant recombinant omega-1 protein (rω-1), which demonstrates similar functions to natural ω-1, induced T-cell populations that were less sensitive for HIV-1 R5 infection (p<0.05), but not for X4 virus infection. This inhibition associated again with a reduction in IFN-γ and MIP-1β expression, but additionally correlated with reduced CCR5 expression. We have shown that SEA parasite antigens and more specifically rω-1 can modulate HIV-1 infectivity with the potential to influence disease course in co-infected individuals. ...>