太阳黑子活动对新发病毒性传染病发生的影响

目前科学界认为新发病毒性传染病的出现主要与人类乱捕乱杀野生动物、动物贸易、新农田开垦、城市化进程、人口的快速增长、国际旅游、人口流动、气候变化以及便捷的交通条件等人类活动或生态学因素有关，然而新发病毒性传染病一般只出现在特定的年份，这意味着在这些特定年份一定出现了某种不同寻常的因素，并对传染病的发生起到了决定性作用，因此，只有找到影响传染病发生的决定因素，才能找到新发病毒性传染病发生的根源，从而根据决定因素对未来的新发病毒性传染病进行科学预测和预警。

太阳黑子极值年或前、后一年是新发病毒性传染病发生的一个重要的危险因素。值得注意的是，2002-2003年在中国广东顺德爆发的非典型肺炎（SARS）以及2012年在中东的沙特阿拉伯出现的中东呼吸综合征（MERS），由于2000-2001年以及2011-2014年是太阳黑子活动的双峰年，所以也是发生在太阳黑子活动高峰期。太阳黑子数与太阳的活动密切相关，在太阳黑子峰值年前后，太阳活动到达高峰, 耀斑出现的次数最多, 耀斑辐射出的大量的紫外线、强X射线，以及宇宙线和非高能粒子。而宇宙射线与太阳黑子相对数呈显著的负相关，这主要是由于当太阳处于活跃期的时候，太阳周边的磁场就会变强，来自太阳系外的宇宙射线也会被太阳磁场所遮挡，从而使照射到地球的宇宙射线大大减少；但是如果太阳处于低谷期，则太阳磁场变弱，照射到地球上的宇宙射线自然也就变多。1958-2010年全球共出现28种新发病毒传染病，28种新发病毒传染病中，24种的病原体是具有高变异率的RNA病毒，19种目前已经确定在自然界存在野生动物宿主。目前已发现的大部分新发病毒传染病的病原体是具有高变异率的RNA病毒，对病毒的基因组来说，点突变，基因重组和基因重排被认为是导致新发病毒传染病出现的三种基本的变异机制。引起大流行或者爆发的病毒一般要通过基因重组和基因重排形成新的抗原以逃避人体的免疫系统的阻击，基因重组和基因重排是导致病毒出现的重要机制。基因重组是指当二种有亲缘关系的不同病毒感染同一宿主细胞时，它们的遗传物质发生交换，结果产生不同于亲代的可遗传的子代，称为基因重组（Genetic recombination）。灭活病毒间的重组例如用紫外线灭活的两株同种病毒，若一同培养后，可使灭活的病毒复活，产生出感染性病毒体，此称为多重感染再复活（Multiplicity reactivation），这是因为两种病毒核酸上受损害的基因部位不同，由于重组合相互弥补而得到复活。死活病毒间的重组例如将能在鸡胚中生长良好的甲型流感病毒（如A0或A1亚型）疫苗株经紫外线灭活后，再加亚洲甲型（如A2亚型）活流感病毒一同培养，产生出具有前者特点的A2亚型流感病毒，此称为交叉感染再复活(Cross reactivation)。多重感染再复活以及交叉感染再复活是导致病毒基因重组和基因重排的重要机制，实验室采用紫外线以及伽马射线等辐射分别使流感病毒实现了多重感染再复活以及交叉感染再复活[。同时也初步证明了新发病毒性传染病的发生可能与太阳黑子和宇宙射线有关。另外, 太阳的活动对地球气候有重要影响, 引发飓风、暴雨和严寒等严重气候异常, 并最终会影响到整个生态系统。大部分新发病毒性传染病在自然界存在野生动物宿主，而气候异常可以影响动物的迁徙模式或改变它们的栖息地，进而增加与人类和牲畜接触的机会和患病风险。例如，刚果爆发的致命的埃博拉出血热被证明与迁徙果蝠的大量涌入有很大关系；而马来西亚和澳大利亚的尼帕病毒和亨德拉病毒的爆发与此前迁徙的果蝠的栖息地的改变有关，这些果蝠之前为了寻找暂时的食物来源而进行迁徙，如今它们在终年提供水果的果园定居下来，果园的位置让这些果蝠接近了猪和马，并增加了将病毒传播给人类的风险。而2002-2003年爆发的SARS和2012年出现的MERS的自然宿主均为蝙蝠，蝙蝠本身是一种对食物获得性高度敏感的流动性动物，它们很可能因为食物供给改变栖息地或飞行活动范围，并从森林或洞穴迁徙出来，居住到离果子狸或骆驼更近的地方，而果子狸或骆驼是SARS和MERS病毒的中间宿主，在寻找食物的过程中，这些蝙蝠很可能排放大量的病毒到果子狸或骆驼的日常生活环境中，不断扩大的交叉物种接触很可能促进冠状病毒之间的重组。其它大部分新发病毒传染病在自然界也存在野生动物宿主，在太阳黑子极值年附近，人类如果不断通过各种活动接触携带某些病毒的自然界野生动物或者它们的排泄物，宿主的病原体就可能通过基因重组或基因重排等方式突破原有物种间的屏障，从而成功的在人间引发新发病毒性传染病的流行。

SARS, MERS and the Sunspot Cycle （论文发表在current science）见附件

Abstract

The SARS and MERS outbreaks pose a serious public health threat because of the high case fatality risk. Research on the environmental factors underlying SARS and MERS epidemiology may provide useful insights into the occurrence of SARS and MERS outbreaks. This study suggested that double peaks in the sunspot cycle in 2002 and 2012 were associated with the emergence of SARS and MERS outbreaks. Potential mechanisms by which sunspot activity may influence SARS and MERS outbreaks in humans are discussed. Current and future surveillance efforts should be supported to construct a comprehensive early warning system involving sunspot activity for detecting future SARS and MERS outbreaks as early as possible.

Keywords: SARS; MERS; Sunspot

SARS—a clue to its origins.pdf

In a letter to the Lancet published in 2003 it was suggested¹ that the first outbreak of SARS-CoV in China may have involved a space-borne trigger. The speculation was that this might have taken the form of an RNA segment or cosmic rays that served to alter the genome of an already endemic corona virus.

Corona viruses define a large genus, which contains the largest known genomes for any RNA virus.  Although a benign form of the human corona virus has been known to be present in patients with the common cold and could be regarded as an endemic virus, the puzzle relates to the sudden emergence of its more lethal variants.  The first known case of severe acute respiratory syndrome (SARS) was recorded in Foshan, China in 2002.  The outbreak began in the Guangdong Province and spread to humans supposedly from a reservoir of the virus that had already been established in civet cats and raccoon dogs; it eventually spread to 37 countries around the world². The total number of confirmed cases is 8096 and the average fatality rate close to 10%.

A decade later, in 2012, an outbreak of MERS-CoV occurred in the Middle East with cases of illness spreading sporadically to other countries.  Since September 2012 some 1791 cases were confirmed with an average fatality of 30%.  The source of MERS-CoV is not fully understood but genomic studies suggest an original reservoir in bats that was possibly later extended to include camels².

In relation to the suddenness of emergence of both SARS and MERS, we may ask the following questions: Why did the outbreaks emerge at the time they did? What factor or factors precipitated their emergence? What are the spillover mechanisms from already established reservoirs of virus? How can we seek to predict or perhaps prevent the next outbreak in advance? This study seeks to address these questions.

The unsolved mystery relates to the cause of the sudden genomic change that evidently occurred in an endemic Corona virus, first in 2002 leading to SARS-CoV, and later in 2012 leading to MERS-CoV.  One might consider several possible causes:

(a)    spontaneously occurring mutations

(b)   mutations induced by ionizing radiation – cosmic rays or solar X-rays

(c)    hybridization involving recombination with a virus/virion component of external origin.

We consider (a) to be an unlikely option.  In cases (b) and (c) a connection with the sunspot cycle could be anticipated, since dramatic changes in solar activity could both cause changes in the flux of ionizing radiation that reaches Earth whilst also creating gateways for the rapid descent of nanometer sized virions of possible cometary origin from a stratospheric reservoir.  Hope-Simpson³and Qu⁴ have already demonstrated that a connection exists between influenza pandemics and extrema (maxima or minima) in sunspot numbers. Furthermore，sunspot activity in extrema years was identified as an important risk factor in influenza pandemics⁴.

In Fig. 1 we show the smoothed out sunspot numbers from 1950-2015 with points representing the dates of onset of SARS-CoV and MERS-CoV.  We note that both these events coincide with double peaks in the sunspot cycle, the first in 2002 and the second in 2012. Sunspot numbers are strongly correlated with solar activity, such as X-ray flares and total irradiance of the sun. Increased numbers of solar flares and coronal mass ejections produce numerous high-energy solar particles during the solar maximum period.

Point mutations, gene recombination, and gene reassortment are thought to be the three basic mechanisms of viral emergence. Solar radiations are physical mutagens leading to natural point mutation and can lead to the emergence of new viruses.  Recombination and reassortment of viral genes occur at highly variable frequencies in viruses with RNA as their genetic material. Multiplicity reactivation and cross reactivation have also been proven to be general mechanisms of genetic recombination. Such reactivation has been observed in influenza viruses irradiated by various types of radiations, such as ultraviolet light and gamma ray, in laboratories during the 1950s to the 1960s.  Most significantly, in our particular case, genetic data reveal that SARS-CoV and MERS-CoV are recombinants^5,6, and therefore recombination events were probably responsible for the outbreaks of SARS and MERS. The recombination involved a gene component that was either introduced from and external source or activated by events linked to the sunspot cycle as seen in Fig. 1. 

Sunspot activity in the maximum or minimum phase can significantly impact the Earth’s climate, thereby causing extreme climate events, such as high temperature, droughts, and severe cold^7-10. Strong scientific evidence points to the bats as the natural reservoirs for SARS-CoV and MERS-CoV. These bats are highly mobile, samples large volumes of air, and are seasonally nomadic in response to local food availability. They also probably shift habitats or expand their scope of activities prompted by changes in food availability or habitat suitability that are in turn influenced by extreme climate events. These bats may migrate from the forests or caves and live closer to other animal populations such as civet cats. Civet cats and camels are considered the intermediate hosts of SARS-CoV and MERS-CoV. The migrating bats can shed large quantities of coronavirus to their common living environment in their pursuit of food. In this process the enhanced frequency of interspecies contacts can facilitate genetic recombination of any circulating coronavirus components.

Solar radiation can inactivate coronaviruses, but the resulting seemingly non-infectious inactivated viruses are in fact semi-infectious. Recombination is the process by which interspecies mixing of coronaviruses can exchange genetic material. For recombination to occur, co-infection with two or more coronavirus strains is necessary. Semi-infectious particles deliver an incomplete set of viral genes to the cell that can, however, support a full cycle of replication.  

Finally, we note that some “new” coronaviruses appear to have successfully acquired the ability to spread from animal hosts to humans through various human activities such as the breeding or slaughter of civet cats and camels.  In the longer term changes in solar activity and the intensity and frequency of sunspots could impact global warming and climate change¹¹. Global warming can directly affect the ability of individual bats to detect prey and indirectly their interspecies interactions with competitors and prey¹².

In conclusion we make the bold suggestion is that an approach to a double peak in the sunspot cycle may serve as a potential forewarning of future pandemics.  Together with other epidemiological data this could be a useful factor for strategic disease control planning.

References

1.   Wickramasinghe C, Wainwright M.  Narlikar J. SARS-a clue to its origins?, The Lancet, 2003; 361, 1832

2.  De Wit E, van Doremalen N, Falzarano D, Munster VJ. SARS and MERS: recent insights into emerging coronaviruses, Nature Reviews: Microbiology,  2016;14(8):523-534

3.    Hope-Simpson RE, Sunspots and flu: a correlation. Nature, 1978; 275:86.

4.    Qu J. Is sunspot activity a factor in influenza pandemics?. Rev. Med. Virol., 2016;  26(5):309-313.

5. Su S, Wong G, Shi W, et al. Epidemiology, Genetic Recombination, and Pathogenesis of Coronaviruses.Trends Microbiol. 2016; 24(6):490-502.

6.   Sabir JS, Lam TT, Ahmed MM, et al. Co-circulation of three camel coronavirus species and recombination of MERS-CoVs in Saudi Arabia. Science. 2016; 351(6268):81-84. 

7.  Ineson S, Scaife AA, Knight JR, et al. Solar forcing of winter climate variability in the Northern Hemisphere. Nat Geosci .2011; 4: 753-757.

8. Stager JC, Ryves D, Cumming BF, et al. Solar variability and the levels of Lake Victoria, East Africa, during the last millennium. J Paleolimnol 2005; 33:243–251.

9. Stager JC, Ruzmaikin A, Conway D, et al. Sunspots, El Niño, and the levels of Lake Victoria, East Africa. J Geophys Res 2007;112:15.

10 Gachari F, Mulati DM, Mutuku JN.Sunspot numbers: Implications on Eastern African rainfall. S. Afr. j. sci 2014; 110:1-5.

11. Gupta R,Gilalana LA,Yaya OS. Do sunspot numbers cause global temperatures? Evidence from a frequency domain causalitu test. AppliedEconomics. 2014,47(8):798-808.

12. Luo J ,Koselj K ,Zsebok S ,Siemers BM ,Goerlitz HR . Global warming alters sound transmission: differential impact on the prey detection ability of echolocating bats. J. R. Soc. Interface . 2004;11: 20130961.

SARS, MERS and the sunspot cycle.pdf