Cientistas da Northwestern Medicine descobriram como o HIV sequestra processos intracelulares para proliferar e contribuir para a neurodegeneração, de acordo com um novo estudo publicado na Nature Communications .
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)
Modelo de como Gag e C99 competem pelo controle das vias de triagem vesicular. Crédito: Nature Communications (2023). DOI: 10.1038/s41467-023-40000-x
Cientistas da Northwestern Medicine descobriram como o HIV sequestra processos intracelulares para proliferar e contribuir para a neurodegeneração, de acordo com um novo estudo publicado na Nature Communications .
Mais de 39 milhões de pessoas em todo o mundo viviam com HIV no final de 2022, segundo dados da Organização Mundial da Saúde. Atualmente, o tratamento para pessoas vivendo com HIV consiste em medicamentos anti-retrovirais que reduzem a quantidade de vírus no corpo, mas não necessariamente previnem a propagação ou curam a infecção.
Além de causar a síndrome da imunodeficiência adquirida (AIDS), o vírus da imunodeficiência humana tipo 1 (HIV-1) entra no sistema nervoso central em cerca de 80% dos indivíduos infectados, resultando em dano neuronal que muitas vezes leva a distúrbios neurocognitivos associados ao HIV (comumente abreviado como HAND), disse Mojgan Naghavi, Ph.D., professor de Microbiologia-Imunologia e autor sênior do estudo.
"Embora o HIV-1 não infecte neurônios, ele infecta células mielóides residentes no cérebro, como macrófagos e microglia. No entanto, como e por que a infecção por HIV-1 causa condições como HAND permanece enigmático", disse Naghavi, que também é um membro do Robert H. Lurie Comprehensive Cancer Center da Northwestern University.
Pesquisas anteriores do laboratório de Naghavi revelaram que a proteína precursora de amilóide (APP) é altamente expressa em macrófagos e microglia e restringe a replicação do HIV-1. Para neutralizar isso, o HIV-1 promove o processamento de APP que, em última análise, resulta na produção de beta-amilóides tóxicos que contribuem para HAND, de acordo com a pesquisa anterior de Naghavi.
Acredita-se que o acúmulo de beta-amilóides seja um dos principais contribuintes para a neurodegeneração em uma variedade de doenças associadas à demência, incluindo a doença de Alzheimer, mas como e por que o beta-amilóide é produzido em pacientes infectados pelo HIV e sua contribuição para HAND permaneceu um mistério, disse Naghavi.
No estudo atual, Naghavi e seus colaboradores procuraram identificar os mecanismos subjacentes da função antiviral do APP.
“Abordamos essas questões e, ao fazê-lo, superamos uma segunda questão fundamental na biologia da doença, fornecendo informações sobre aspectos únicos, mas pouco compreendidos, da replicação do HIV-1 em tipos específicos de células imunológicas”, disse Naghavi.
Naghavi e seus colaboradores descobriram que o processamento de APP ocorre dentro de subconjuntos de corpos multivesiculares (MVBs) que também são necessários para a replicação do HIV-1, de acordo com o estudo.
Em condições normais, o processamento amiloidogênico classifica esses MVBs em lisossomos, organelas que eliminam os resíduos celulares. Isso limpa os amilóides e reprime a replicação do HIV-1. Para combater isso, o HIV-1 desvia a triagem de MVB dos lisossomos para vias exocíticas que suportam sua replicação, mas também aumenta a secreção de beta-amilóide.
Depois de fazer essa descoberta, Naghavi e seus colaboradores trataram células cultivadas com um inibidor clinicamente aprovado da via de processamento de APP e descobriram que ele bloqueou com sucesso o acesso do HIV-1 aos MVBs, suprimindo assim a replicação viral na micróglia e macrófagos.
As descobertas apontam para esta via como um alvo terapêutico potencial para distúrbios neurocognitivos associados ao HIV, disse Naghavi.
Naghavi observou que as descobertas têm o potencial de informar o uso de inibidores clinicamente aprovados que podem um dia ser usados ??para tratar HAND. Avançando, Naghavi e seus colaboradores continuarão a estudar a relação entre HIV-1 e APP.
“Atualmente, estamos tentando entender como o HIV-1 e o APP influenciam a localização e a função vesicular um do outro e, portanto, o destino do vírus infeccioso e da produção de amiloide tóxico”, disse Naghavi.
Mais informações: Feng Gu et al, HIV-1 promove a ubiquitinação do fragmento amiloidogênico C-terminal de APP para apoiar a replicação viral, Nature Communications (2023). DOI: 10.1038/s41467-023-40000-x
Informações do jornal: Nature Communications