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病毒如何進入細胞?它們的感染策略決定了是否能跨越物種或引發大流行病

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COVID-19, flu, mpox, noroviral diarrhea: How do the viruses that cause these diseases actually infect you?

2019冠狀病毒症(COVID-19Coronavirus Disease-19)、流感、猴豆(mpoxmonkeypox)、諾羅病毒腹瀉:導致此些疾病的病毒,實際上如何感染人們?

 

Viruses cannot replicate on their own, so they must infect cells in your body to make more copies of themselves. The life cycle of a virus can thus be roughly described as: get inside a cell, make more virus, get out, repeat.

病毒無法自行複製。因此,它們必須感染人們體內的細胞,來能產生更多自身的複製。因此,病毒的生命週期,大致上能被描述為:進入細胞內,產生更多病毒,退出,重複。

 

Getting inside a cell, or viral entry, is the part of the cycle that most vaccines target, as well as a key barrier for viruses jumping from one species to another. My lab and many others study this process to better anticipate and combat emerging viruses.

進入細胞內,也就是病毒進入,除了病毒從一個物種躍進到另一個物種的關鍵障礙之外,也是大多數疫苗鎖定之循環的一部分。我的實驗室及許多其他實驗室研究這個過程,來更佳地預測及對抗新出現的病毒。

 

Different viruses travel into the body in various ways – via airborne droplets, on food, through contact with mucous membranes or through injection. They typically first infect host cells near their site of entry – the cells lining the respiratory tract for most airborne viruses – then either remain there or spread throughout the body.

不同的病毒以,經由空氣中的飛沫、食物、透過接觸黏膜或注射等,不同方式進入人體內。通常,它們首先感染靠近其進入部位的宿主細胞(對大多數空氣傳播之病毒而言,是作為呼吸道襯裡的細胞),然後不是停留在那裡,就是擴散到全身。

 

Viruses recognize specific proteins or sugars on host cells and stick to them. Each virus gets only one shot at putting its genome inside a cell – if their entry machinery misfires, they risk becoming inactivated. So they use several mechanisms to prevent triggering entry prematurely.

病毒識別宿主細胞上的特定蛋白質或糖類,然後黏附其上。每種病毒只有一次機會,將其基因體注入細胞內。倘若它們的進入機制失靈,則冒有變鈍化的風險。因此,它們使用多種機制,來防止過早誘發進入。

 

After the virus binds to the cell, specific molecules on the cell’s surface or within the cell’s recycling machinery activate viral coat proteins for entry. An example is the SARS-CoV-2 spike that COVID-19 vaccines target.

在病毒與細胞結合後,於細胞表面上或細胞回收機制內的特定分子,活化病毒外殼蛋白以備進入。一個例子是COVID-19疫苗鎖定的第二型嚴重急性呼吸系統徵候群-冠狀病毒(SARS-CoV-2Severe Acute Respiratory Syndrome Coronavirus-2)棘突。

 

These proteins need to modify the cell membrane to allow the viral genome to get through without killing the cell in the process. Different viruses use different tricks for this, but most work like cellular secretion – how cells release materials into their environment – in reverse.

在此過程中,此些蛋白質必需修飾細胞膜,來使病毒基因體得以通過,而不會殺死細胞。為此,不同的病毒使用不同的技巧。不過,大多數病毒以相反之如細胞的分泌,將物質釋放到其環境中般運作。

 

Specialized viral proteins help merge the membranes of the virus and the cell together and release the viral core into the interior of the cell.

諸多經特化的病毒蛋白有助於,將病毒膜與細胞融合在一起,並將病毒核心釋放到細胞內部。

請參閱原文短片:https://youtu.be/i__QSjC-pt0

This animation depicts HIV fusing its membrane with a cell in order to release its contents inside.

此動畫描繪了,為了釋出其內部的內含物,人類免疫缺陷病毒(HIVHuman Immunodeficiency Virus)將其膜與細胞融合。

 

At this point, the viral genome can enter the cell and start replicating. Some viruses use only the cell’s machinery to replicate, while others carry along portions of their own replication machinery and borrow some parts from the cell. After replicating their genomes, viruses assemble the components required to make new viruses.

在此時,病毒基因體能進入細胞,並開始複製。有些病毒僅使用該細胞的機制進行複製,而其他病毒隨身攜帶部分其自身複製機制,並從細胞借一些部分。複製其基因體後,病毒組合產生新病毒所需的成分。

 

Two central questions scientists are studying about viral entry are how your body’s defenses can disrupt it and what determines whether a virus from other species can infect people.

有關病毒的進入,科學家們正在研究的兩個核心問題是,人體的防禦如何能瓦解病毒,及什麼決定來自其他物種的病毒,是否能感染人類。

 

Your body has a multilayered defense system against viral threats. But the part of your immune system called the antibody response is generally thought to be most effective at sterilizing immunity – preventing an infection from taking hold in the first place as opposed to just limiting its scope and severity.

人體具有對抗病毒威脅的多層防禦系統。不過,被稱為抗體反應部分的免疫系統,通常被認為,在殺菌免疫力上,是最有效的。與僅限制其範圍及嚴重程度完全不同,這首先就防止了感染發生。

 

For many viruses, antibodies target the part of the virus that binds to cells. This is the case not just for current COVID-19 vaccines but also the majority of immunity against influenza, whether from vaccines or from prior infection.

對諸多病毒而言,抗體鎖定病毒與細胞結合的部分。這不僅適用於目前的 COVID-19疫苗,也適用於大多數對抗流感的免疫力,無論是來自疫苗或是先前的感染。

 

However, some antibodies target the entry machinery instead: Rather than preventing the virus from sticking, they prevent the virus from working altogether. Such antibodies are often harder for the viruses to escape from but are difficult to reproduce with vaccines. For that reason, developing antibodies that inhibit cell entry has the been the goal of many next-generation vaccine efforts.

然而,有些抗體反而鎖定進入機制:不是阻止病毒黏附,而是完全阻止病毒起作用。對病毒而言,這種抗體通常較難逃脫。不過,難以使用疫苗來複製。為了那原因,開發抑制細胞進入的抗體,一直是諸多下一代疫苗的努力目標。

 

1. 此圖顯示,四種不同類別的抗病毒藥物,如何抑制愛滋病毒。 一種阻止病毒進入細胞,三種抑制不同的病毒酵素。

This diagram shows how four different classes of antiviral drugs inhibit HIV. One stops viruses from entering cells, and three inhibit different viral enzymes.

 

The other key question researchers are asking about viral entry is how to tell when a virus from another species poses a threat to people. This is particularly important because many viruses are first identified in animals such as bats, birds and pigs before they spread to humans, but it’s unclear which ones may cause a pandemic.

有關病毒進入的另一個關鍵問題,研究人員們問起的是,如何判斷來自其他物種的病毒,何時對人類構成威脅。這特別重要,因為諸多病毒,在散播到人類前,首先於諸如蝙蝠、鳥類及豬等動物中,被確認。不過,哪些病毒可能引發大流行病,則不詳。

 

The part of viruses that stick to human cells varies the most across species, while the part that gets the virus into cells tends to stay mostly the same. Many researchers have thought that viruses changing in ways that bind better to human cells, like influenza viruses that bind to cells in the nose and throat, are some of the most important warning signs for pandemic risk.

病毒黏附於人體細胞上的部分,在不同物種之間差異最大,而將病毒帶入細胞的部分,傾向幾乎皆相同。許多研究人員一直認為,病毒以更佳與人類細胞結合的方式發生變化,譬如與鼻子及喉嚨細胞結合的流感病毒,是大流行病風險的一些最重要警訊。

 

However, coronaviruses – the family of viruses containing SARS-CoV-2 – are prompting re-examination of that idea. This is because several animal coronaviruses can actually bind to human cells, but only a few seem to be able to transmit well between people.

然而,冠狀病毒(包含SARS-CoV-2的病毒家族)正在促使人們重新審視那想法。這是因為若干動物冠狀病毒,實際上能與人類細胞結合。不過,似乎只有少數能在人與人之間順利傳播。

 

Only time will tell whether researchers need to broaden their pandemic prevention horizons or if their current prioritization of risky viruses is correct. The one grim reality of pandemic research, like earthquake research, is that there will always be another one – we just don’t know when or where, and we want to be ready.

只有時間能告知研究人員們,是否需要擴大其流行病預防範圍,或目前他們有關危險病毒的優先順序是否正確。如同地震研究,流行病研究的一項嚴峻現實是,總是會有另一種病毒出現。我們只是不知道何時或何地,不過我們想做好準備。

 

 

網址:https://theconversation.com/how-do-viruses-get-into-cells-their-infection-tactics-determine-whether-they-can-jump-species-or-set-off-a-pandemic-216139

翻譯:許東榮

台長: peregrine
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