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Seleção Natural e a Evolução do Vírus SARS-CoV-2

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Partículas do vírus SARS-CoV-2 dentro de endossomos

Novas variantes do SARS-CoV-2, o vírus que causa o COVID-19, surgem por meio de mutações quando o vírus se replica nas células de um hospedeiro infectado. Crédito: NIAID

A natureza é analógica. Não é um sistema binário. No mundo dos vivos não há interruptores explícitos que liguem ou desliguem os sistemas discretamente. Em vez disso, a natureza ajusta os sistemas por meio de mostradores analógicos, como um rádio antigo – mudando gradualmente as variáveis ​​para alcançar equilíbrio e equilíbrio para garantir que a vida seja sustentável e continue.

A evolução prossegue dessa maneira, com novas formas de vida aparecendo e algumas desaparecendo ao longo de milênios – ou, no caso de patógenos microbianos (vírus, bactérias e parasitas) ao longo de dias ou semanas.

A mudança evolutiva resulta de duas forças opostas: A seleção positiva reproduz variações genéticas benéficas que permitem que o vírus sobreviva, enquanto a pressão de seleção negativa dificulta a sobrevivência e a capacidade de reprodução do vírus.

A evolução pode ser estudada no nível molecular. Para muitos anos, minha pesquisa foi focado em a tripanossoma africanoa parasita responsável pela doença do sono africana.

Variação antigênica

Os tripanossomas vivem na corrente sanguínea de seus hospedeiros mamíferos (incluindo humanos) e as primeiras observações de seus números mostraram um padrão consistente de aumento de onda seguido por números decrescentes e, depois de uma semana ou mais, números crescentes novamente.

Curva de crescimento da tripanossomíase africana

Curva de crescimento da tripanossomíase africana em um humano infectado. Ross, R., & Thomson, D. (1910). Um Caso de Doença do Sono mostrando Aumento Periódico Regular dos Parasitos Divulgados. Crédito: Br Med J, 1(2582), 1544-1545. https://doi.org/10.1136/bmj.1.2, CC BY-NC

Os tripanossomas são vulneráveis ​​aos anticorpos produzidos pelo sistema imunológico do hospedeiro, que se ligam ao parasita e o eliminam. Essa resposta imune faz com que os números de tripanossomas diminuam, conforme ilustrado pelos pontos baixos do padrão de onda. Mas antes que os tripanossomas desapareçam completamente, seus números aumentam novamente e a onda se repete.

Esse intrigante padrão de crescimento gerou muito interesse e pesquisa em meu laboratório e, por fim, descobrimos que o parasita pode alterar sua identidade molecular para escapar dos anticorpos do hospedeiro antes de ser completamente eliminado. Isso significa que a população de tripanossomas responsável por cada um dos picos de onda é uma variante distinta de todas as outras. Anticorpos dirigidos contra uma variante não têm efeito nas variantes subsequentesentão o padrão de onda continua.

A estratégia muito bem sucedida do tripanossoma evoluído para ajudá-lo a sobreviver em face da pressão de seleção negativa constante de anticorpos. Esse mecanismo que ajuda um parasita ou patógeno a escapar do sistema imunológico do hospedeiro é chamado de variação antigênica.

As ondas do COVID-19 são semelhantes à doença do sono

Lembro-me da curva de crescimento dos tripanossomas ao observar o padrão da contagem de casos canadenses a partir do atual[{” attribute=””>COVID-19 pandemic.

 COVID-19 Case Counts Canada

Case counts of COVID-19 in Canada since January 25, 2020. Credit: N. Little. COVID-19 Tracker Canada (2020)

The peaks in cases reflect the arrival of new variants, the most recent of which is omicron, the variant now circulating most widely globally.

The strategy used by SARS-CoV-2, the virus that causes COVID-19, is similar to the trypanosome’s, although the mechanism for generating novel variants is quite different. For the virus, new variants arise by mutation in genes that encode the so-called “spike protein,” the part of the virus that enables it to enter cells and infect people.

Mutations arise due to “errors” that occur when the virus is replicating itself in the cells of the host’s respiratory system. Because the virus has a mechanism that can attempt to repair the “errors,” SARS-CoV-2 evolves more slowly than the trypanosome. It evolves more slowly because the virus has a mechanism that can try to repair the “errors.” However, this repair process is not perfect, and some mutations get retained.

If mutations result in a spike protein distinct from any other variant preceding it, we will see a new variant appearing. The omicron variant is particularly interesting (and somewhat ominous) because of its high number of mutations, not only in the spike protein but in other viral genes as well.

SARS-CoV-2 Virus Particle

The red projections seen on the outside of the SARS-CoV-2 virus are spike proteins, which enable the virus to attach to and infect host cells, and then replicate. Credit: NIAID

By employing this strategy of antigenic variation, the survival of the SARS-CoV-2 virus is assured. So, the appearance of new variants is due to mutations that represent the positive selection force: genetic variations that help the organism get reproduced.

The decline of case numbers during a pandemic is due to negative selection forces. These include effective public health interventions that limit the spread from one person to the next (such as masks), as well as the hosts’ immune response (antibodies) resulting from either infection, vaccination or both.

An infected person will, over time, generate antibodies against the virus and begin to eliminate that variant, like in the trypanosome case. But because SARS-CoV-2 mutations occur slowly, the virus needs to find a new, non-immune person to carry on. In order to find new non-immune hosts, the virus induces symptoms that help it to spread: the coughing and sneezing that enable it to jump from one person to the next via droplets.

Antibodies and illness

Given the capacity of SARS-CoV-2 to mutate, there are certainly new variants arising continuously. However, if medical and public health interventions are successful in reducing transmission between infected and uninfected/unvaccinated people, it is quite possible that the virus will evolve to generate a less virulent variant that could establish itself as an endemic infection producing mild symptoms.

When people infected with a pathogenic microbe experience symptoms of illness, those symptoms often serve a purpose: they can contribute to either the microbe’s survival or the survival of the infected host. A classic case is diarrhea resulting from infection with cholera or from amoebic dysentery. Both infections produce life-threatening diarrhea, but the symptom serves different purposes in each disease.

SARS-CoV-2 Alpha Variant Virus Particles

Transmission electron micrograph of alpha variant SARS-CoV-2 virus particles. Credit: NIAID

In the case of cholera, this symptom serves the microbe because it enables the bacteria to exit the host’s body and, in places with poor sanitation, contaminate the water supply and transmit to new hosts. In the case of amoebic dysentery, the symptom is a result of the host’s body attempting to rid itself of the infection.

Clinicians must be able to distinguish between these two scenarios in the management of infectious diseases in order to avoid contributing to the problem rather than solving it. In the case of COVID-19, clinical symptoms like sneezing and coughing that enable the virus to spread through the air are positively selecting variants that help the virus spread to new, susceptible individuals (such as unvaccinated people).

That means measures like masking, social distancing, and vaccination can impede spread by helping to prevent aerosol transmission.

Continued efforts to achieve a fully vaccinated population are crucial. The unvaccinated and the uninfected are ideal hosts for SARS-CoV-2, and ideal for generating new variants due to the absence of negative selection by antibodies, which makes it easier for the virus to replicate and produce new mutations.

Although nature may move slowly in an analog manner, humans can flip binary switches and we can act now to ensure global vaccine equity. Ensuring global vaccine coverage is not only imperative from an evolutionary perspective but is clearly the ethical option as well.

Written by Michael Clarke, Adjunct Professor, Interfaculty Program in Public Health, Schulich School of Medicine and Dentistry, Western University.

This article was first published in The Conversation.The Conversation





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