1 00:00:08,310 --> 00:00:12,450 In our airways, the air we breathe comes into contact with a mixture of different 在人类呼吸道,空气会经过并接触到 2 00:00:12,450 --> 00:00:14,610 types of healthy respiratory cells. 不同类型的呼吸道健康细胞。 3 00:00:16,200 --> 00:00:19,890 Some respiratory cells have hair-like structures that move the mucus along. 有些呼吸道细胞有纤毛结构,用于推动粘液。 4 00:00:19,890 --> 00:00:24,190 SARS-CoV-2 coronavirus targets these hairy cells. SARS-CoV-2病毒针对这些纤毛细胞。 5 00:00:26,550 --> 00:00:28,320 The virus itself is deceptively simple. 这种病毒看上去非常简单。 6 00:00:28,920 --> 00:00:32,519 It consists of only a few parts, but together these parts 只包含几个部分,但是这些部分合在一起 7 00:00:32,519 --> 00:00:34,560 create a highly effective virus. 构成了非常高效的病毒。 8 00:00:35,790 --> 00:00:39,660 It has an outer membrane with three types of proteins on it, spike 病毒外层是一层膜结构,上面镶嵌了三种蛋白质: 刺突蛋白, 9 00:00:40,650 --> 00:00:43,320 envelope and membrane proteins. 包膜蛋白和膜蛋白。 10 00:00:46,050 --> 00:00:49,710 Inside the virus, an assembly of nucleocapsid proteins hold 在内部,一系列核壳蛋白将遗传物质 11 00:00:49,710 --> 00:00:51,269 together its genetic material. 包裹其中。 12 00:00:51,870 --> 00:00:53,820 A single strand of viral RNA. 遗传物质是单链病毒RNA。 13 00:00:54,360 --> 00:00:59,190 The spike protein is responsible for making contact with the host 刺突蛋白负责跟宿主细胞进行接触, 14 00:00:59,190 --> 00:01:00,960 cell and starting the infection. 开启感染过程。 15 00:01:01,800 --> 00:01:05,375 It has a coat of sugars that hides it from the body's immune system. 刺突蛋白附有糖基结构,使宿主免疫系统难以识别。 16 00:01:06,465 --> 00:01:10,995 Many of the variants of SARS-CoV-2 are characterized by mutations on SARS-CoV-2有很多结构变化,特征就是发生在刺突蛋白 17 00:01:10,995 --> 00:01:13,215 this spike protein, seen here in red. 上的变异,在这里显示为红色。 18 00:01:14,835 --> 00:01:18,195 These mutations can influence its function, some making 这些变异能够影响刺突蛋白的功能,有些 19 00:01:18,200 --> 00:01:19,725 the virus more infectious. 变异能够增强病毒的传染性。 20 00:01:20,865 --> 00:01:26,805 Many mutations are unique to each variant, but some, like D614G, are found 有些可变结构在不同的毒株中各不相同,但另外一些结构,比如 这里的D614G, 21 00:01:26,805 --> 00:01:28,635 in each of the variants of concern. 则在受关注毒株中反复出现。 22 00:01:32,280 --> 00:01:36,870 When the virus closes in on a host cell, its spike proteins open up and 当病毒接近宿主细胞时,表面的刺突蛋白会打开 23 00:01:36,870 --> 00:01:38,940 bind to a receptor on the host cell. 跟宿主细胞上的受体结合在一起。 24 00:01:40,680 --> 00:01:43,650 The outer part of the spike protein is then cut off by a 而后刺突蛋白的外部结构被 25 00:01:43,650 --> 00:01:45,540 protein on the host cell membrane. 宿主细胞膜上的蛋白结构切去。 26 00:01:47,610 --> 00:01:51,420 This frees the inner core of the spike protein, which is cut open. 这使得刺突蛋白的内部结构暴露出来, 27 00:01:53,430 --> 00:01:57,420 The spike protein then unfurls and anchors into the host cell, 其内部可以展开,并钩上宿主细胞, 28 00:01:59,400 --> 00:02:02,820 pulling the virus closer until the cell membrane and the viral 然后将病毒跟宿主细胞膜拉近, 29 00:02:03,220 --> 00:02:07,050 membrane fuse, allowing the viral genome to enter the host cell 直到病毒包膜跟宿主细胞膜融合,病毒的 基因组得以进入宿主细胞。 30 00:02:15,120 --> 00:02:19,320 Inside the cell a ribosome meets the viral RNA and starts 在细胞内部,某个核糖体碰上病毒RNA,开始 31 00:02:19,320 --> 00:02:21,149 to translate its genetic code. 翻译病毒的基因代码。 32 00:02:22,079 --> 00:02:24,869 The result is a long protein chain containing 得到一个包含无结构蛋白(nsps)的长链 33 00:02:24,869 --> 00:02:27,720 non-structural proteins or nsps. 34 00:02:28,920 --> 00:02:32,700 Initially, these nsps are all attached to one another, but some of 一开始,这些无结构蛋白连接在一起,但是有些 35 00:02:32,700 --> 00:02:35,100 the nps are able to cut the chain. 无结构蛋白能够将长链切开, 36 00:02:36,180 --> 00:02:41,580 The result of this cutting is the release of another nsp, which is able to grab onto 使得另一种非结构蛋白被释放出来,这中非结构蛋白能够 37 00:02:41,580 --> 00:02:47,700 a ribosome and occupy it in such a way that the ribosome can only read viral RNA 附着并占据核糖体,使得他们只能读取病毒RNA 38 00:02:48,345 --> 00:02:50,745 and not the host cells own RNA. 而不再读取宿主细胞自己的RNA。 39 00:02:51,315 --> 00:02:55,005 This means that the virus takes over the cell's protein production 这样病毒就控制了细胞的蛋白质生产机制 40 00:02:55,005 --> 00:02:59,085 machinery, turning the host cell into a virus building factory. 将宿主细胞变成了病毒加工厂。 41 00:02:59,985 --> 00:03:04,575 Meanwhile, the long protein chain is cut into individual nsps. 与此同时,长链蛋白继续被切分成单个非结构蛋白(nsps), 42 00:03:05,445 --> 00:03:09,045 Eventually, the production of nsps stops due to the presence 直到核糖体读取到 43 00:03:09,135 --> 00:03:11,625 of a knot in the viral RNA. 病毒RNA中的一个纽结结构。 44 00:03:12,855 --> 00:03:17,085 This prevents the remaining RNA, which codes for the machinery involved 纽结结构使得后续的RNA——可以生成 45 00:03:17,085 --> 00:03:20,475 in duplicating the viral genome from passing through the ribosome. 复制病毒基因组所必需的蛋白质器件——无法被核糖体读取。 46 00:03:23,895 --> 00:03:27,555 A protein production can either stop here, or the knot in the 蛋白质合成可以停在这里,也可以在纽结结构打开 47 00:03:27,560 --> 00:03:32,175 viral RNA can slip, allowing the remaining viral RNA to be read. 之后继续,使后续病毒RNA也可以被读取。 48 00:03:35,010 --> 00:03:39,450 Because of the knot, the translation of the viral RNA often stops prematurely. 由于纽结的存在,病毒RNA的翻译经常提前结束。 49 00:03:41,640 --> 00:03:46,170 This is an ingenious way for the virus to control how many proteins are being made. 这是病毒控制蛋白质合成的机制。 50 00:03:46,920 --> 00:03:52,230 More of the membrane modifying nsps from before the knot and fewer of the RNA 纽结之前的RNA产生更多的膜修饰nsps越多, 51 00:03:52,230 --> 00:03:54,240 processing nsps from after the knot. 纽结之后的RNA产生的,用来处理RNA的nsps就越少。 52 00:03:56,490 --> 00:03:59,820 The nsps that are embedded into the membrane cause it to curve. 这些nsps镶嵌于细胞膜上,改变了细胞膜的平坦状态, 53 00:04:00,510 --> 00:04:02,340 This disrupts the flat shape of the. 导致细胞膜卷曲, 54 00:04:03,030 --> 00:04:07,760 And creates a structure called a double membrane vesicle or DMV. 从而产生一种叫做DMV的膜结构。 55 00:04:08,880 --> 00:04:12,840 These DMVs create a safe, enclosed environment for the DMV为病毒基因组的复制提供了 56 00:04:12,840 --> 00:04:14,220 viral genome to be copied. 安全的封闭空间。 57 00:04:15,179 --> 00:04:19,230 Inside the DMV several nsps combine to form the machinery 在DMV内部,一些非机构蛋白(nsps)结合在一起, 58 00:04:19,409 --> 00:04:21,450 to create new viral RNA. 形成可以产生新的病毒RNA的结构。 59 00:04:22,409 --> 00:04:26,010 Firstly, a complimentary strand is made to act as a reference. 首先,会产生一条跟病毒RNA互补的RNA链条 60 00:04:27,015 --> 00:04:31,094 This reference then becomes the template for a new strand identical 作为参考模版,根据这个模版,可以 61 00:04:31,094 --> 00:04:32,805 to the original viral genome. 生成跟原病毒RNA一样的RNA基因组。 62 00:04:33,465 --> 00:04:36,675 In addition to the full length viral genome, a set of shorter 除了全长的病毒基因组之外,还会生成一些 63 00:04:36,675 --> 00:04:38,475 RNA strands is also created. RNA片段。 64 00:04:38,775 --> 00:04:43,305 These shorter strands are called subgenomic RNA and will be processed 这些片段称为次基因组RNA,他们会被 65 00:04:43,310 --> 00:04:48,105 by the host cell to create the proteins that go into the new viral particle. 宿主细胞加工,合成病毒颗粒所需要的蛋白质, 66 00:04:48,785 --> 00:04:53,645 The subgenomic RNA exits the DMV through an nsp pore. 这些次基因组RNA通过nsp形成的孔结构离开DMV, 67 00:04:54,255 --> 00:04:58,245 After exiting, it makes its way back to a ribosome and is translated 到达核糖体,被翻译成新的SARS-CoV-2病毒 68 00:04:58,425 --> 00:05:02,634 to make the main proteins that will constitute the new SARS-CoV-2 所需要的蛋白质: 69 00:05:02,655 --> 00:05:08,984 viral particle, a spike envelope membrane and nucleocapsid proteins. 刺突蛋白,包膜蛋白和核壳蛋白。 70 00:05:09,645 --> 00:05:13,544 The newly created nucleocapsid protein sits right by the DMV 新生成的核壳蛋白停留在DMV孔洞旁边 71 00:05:13,544 --> 00:05:18,474 pore, ready to grab onto the viral genome RNA as it exits the DMV. 等新的病毒RNA出来的时候就粘附上去。 72 00:05:19,380 --> 00:05:23,670 The nucleocapsid protein then begins packaging the RNA into what will become 然后核壳蛋白开始自组装,把病毒RNA打包成 73 00:05:23,890 --> 00:05:26,130 the contents of the new viral particles. 新的病毒颗粒的内容物。 74 00:05:28,080 --> 00:05:31,950 After the spike envelope and membrane proteins have been made, they go 刺突蛋白、包膜蛋白和膜蛋白生成之后, 75 00:05:31,950 --> 00:05:33,360 to a different part of the cell. 他们会到达细胞的另外位置, 76 00:05:34,800 --> 00:05:38,370 There the membrane proteins are able to catch the nucleocapsid 在这里膜蛋白会吸附核壳蛋白和病毒基因组 77 00:05:38,370 --> 00:05:40,110 proteins and viral genome. 78 00:05:42,240 --> 00:05:46,950 This makes the membrane bend inwards and a new viral particle eventually buds. 使得这部分膜结构向内卷曲,在内部产生完整的病毒颗粒。 79 00:05:50,219 --> 00:05:54,179 When the membrane compartment containing the viral particle fuses with the outer 这种包含病毒颗粒的膜结构跟细胞膜结合, 80 00:05:54,179 --> 00:05:58,979 cell membrane, the viral particles are then released from the cell, but 就会将病毒颗粒释放出细胞, 81 00:05:58,979 --> 00:06:02,799 that's only the first wave of SARS-CoV-2 particles that will be expelled. 这还只是释放出的第一波SARS-CoV-2病毒颗粒, 82 00:06:03,540 --> 00:06:08,310 Eventually the host cell produces so many viral particles that it dies and 最终,宿主细胞会产生非常多的病毒颗粒而后死掉, 83 00:06:08,310 --> 00:06:12,270 releases a whole wave of new virus particles into the surrounding tissue, 将新的病毒颗粒释放到周围的组织中, 84 00:06:12,870 --> 00:06:15,510 ready to spread and infect nearby cells. 感染附近的细胞。 85 00:06:16,290 --> 00:06:20,970 This completes the life cycle of a single SARS-CoV-2 coronavirus. 这就是一个SARS-CoV-2冠状病毒的完整生存周期。