Sunday, March 23, 2014

Nucleus-like viruses and their enzymes

Recent findings in virology have forced biologists to consider many notions that just a few years ago would have seemed heretical and/or science-fiction-like. For example, there is now serious discussion of the possibility that cellular life descended from viruses (the Virus World theory; see also this paper). A growing (but still minority) viewpoint is that viruses should be considered symbionts rather than simply parasites (see the review by Villereal). Some have dared to propose that the eukaryotic cell nucleus actually stemmed from a virus. Others have speculated the reverse: that the large DNA viruses are actually escaped, spore-like nucei. Meanwhile, some say that during an earlier RNA World, viruses became the original inventors of DNA.

There's no question that large viruses of the NCDLV class have nucleus-like properties. Within a short time of infection, these viruses set up a complex structure inside the cell known as the virus factory, and the factory looks a lot like a cell nucleus. The authors of a recent paper on Mimivirus (the famously huge virus that infects freshwater amoeba) admitted that in previous work, they did, in fact, mistake the virus factory for the nucleus. (See photo.)

Which is the nucleus and which is the virus factory? In this photo, VP is a virus particle (of the enormous mimivirus) developing inside Acanthamoeba. A smaller virus factory (S) is just beginning to form on the left.

Macroscopic aspects aside, the large "nucleocytoplasmic" viruses (some of which infect animals and marine life, not just amoeba) bring with them many genes for enzymes that are normally found in a cell nucleus. I'm not talking about genes for DNA polymerases, topoisomerases, etc., but genes that act on small molecules. In a previous post, I mentioned the example of PBCV-1 (a virus that infects the alga Chlorella) having its own gene for aspartate transcarbamylase (ATCase), which is an enzyme that catalyzes the first committed step in pyrimidine synthesis. This enzyme (common to most living things) is predominantly found in the cell nucleus of higher organisms.

There are other examples. Many NCLDV-group viruses have a gene for deoxy-UTP pyrophosphatase, an enzyme that breaks the high-energy phosphates off dUTP so that uracil isn't accidentally incorporated into DNA. One can imagine that after a virus invades a cell and unleashes its nucleases on the cell's own RNA, many ribonucleotides (breakdown products of RNA) will be liberated; and many of these will then be reduced to deoxy-nucleotides (by ribonucleoside-diphosphate reductase) in preparation for viral DNA synthesis. As it happens, dUTP is quite easily incorporated into DNA (and is promiscuous in its Watson-Crick pairing with other nucleobases); the resulting malformed DNA can trigger apoptosis in some cells. The virus takes no chances. It brings its own dUTPase to make sure uracil never gets into its DNA by mistake.

Some viruses bring their own gene for thymidylate synthase, to bring about the conversion of dUMP to dTMP (in other words, methylation of uracil, in its deoxy-ribonucleoside-monophosphate form, to give thymidine monophosphate). Some also have a gene for thymidylate kinase, which converts dTMP (often just called TMP) to dTDP (or TDP).

Yet another "small-molecule" enzyme encoded by large DNA viruses is ribonucleoside-diphosphate reductase (RDPR). This enzyme is fundamental to the whole DNA synthesis enterprise. Its job is to convert ordinary ribonucleotides to the deoxy form that DNA needs. Without this enzyme, you can make RNA but not DNA. So it's typically found in the cell nucleus (in higher organisms).

It turns out, a gene for RDPR is contained in a great many viral genomes. When I did a BLAST search of the protein sequence for Chlorella virus ribonucleoside reductase against the UniProt database of virus sequences, the search came back with 863 hits, spanning viruses belonging not only to the NCDLV class (pox, mimivirus, phycodnaviruses, etc.) but also the Herpesviridae, plus many bacteriophage groups as well. In terms of the sheer variety of virus groups involved, it's hard to think of another "small-molecule-processing" enzyme that spans as many viral taxa. We're talking about everything from relatively small bacteriophages to mimivirus, and lots in between.

The reductase gene is so widespread, it made me wonder what its phylogenetic distribution might look like. In other words: Are viral RDPRs related to each other? Are they related to the host's own RDPR? Does the enzyme's evolution follow the viral path, or the host path?

Just for fun, I obtained a number of ribonucleoside reductase (small subunit) protein sequences for viruses, plants, animals, bacteria, fungi, and various eukaryotic parasites (using the tools at, then fed the results to the tree-maker at What I got was the following "maximum likelihood" phylogenetic tree. (See this paper for details on the tree algorithm. Also, be sure to check out this nifty paper to learn more about how to read this sort of tree.)

For convenience, names of viruses are depicted in blue. Notice how, except for the Vaccinia-Variola group, which is deeply nested, most of the viral nodes are ancestral to most of the higher-organism nodes; you have to go through many levels of viral ancestors to get from the original, universal ancestor (presuming there was one) to the reductase gene of the pig, say. From this diagram, it would appear that the Pox-family reductase gene is derived, in some way, from a highly evolved host. But that's the exception, not the rule. All of the other viral genes are outgroups and/or, more usually, ancestors of one another.

Mimivirus is fairly high up the chain and shows relatedness to two very common freshwater and soil bacteria (Pseudomonas and Burkholderia).

It would be fun to go back and remake the tree, adding more organisms. (If you end up trying this, let me know the results.) For now, I'm comfortable concluding that except for pox-family viruses, the ribonucleoside reductase produced by major DNA viruses and phages are not derived from current-day hosts. A parsimonious (but not necessarily correct!) explanation is that the phage reductases are ancestral to host orthologs; but it is also possible that the phage reductases derive from very ancient hosts (not depicted in the tree), with current-day hosts appearing to derive from phage genes when in fact the similarity is to a long-ago host ortholog. In any case, the tree shows that organismal RDPRs tend to be related to organismal RDPRs and viral versions are related to viral versions. What we don't see anywhere is a viral sub-tree growing out of a host sub-tree (as would be the case if the viral enzymes simply derived from modern host enzymes).

The UniProt identifiers of the protein sequences used in this study are given below in case you want to try to replicate these results (or perhaps extend them). To retrieve the protein sequences in question, go to and click the Retrieve tab, then Copy and Paste the following sequences (one to a line) exactly as shown:



  1. Greetings to the general public, Am Mike Amos i want to inform the public how i was cured of HERPES Simplex Virus by a Doctor called Ero. i visited different hospital but they gave me list of drugs like Famvir, Zovirax, and Valtrex which is very expensive to treat the symptoms and never cured me. I was browsing through the Internet searching for remedy on HERPES and i saw comment of people talking about how Doctor Ero cured them. I Was scared because i never believed in the Internet but i was convince to give him a try because i was having no hope of been cured of HERPES so i decided to contact him on his email that was listed on the comment ( ) i searched his email on net and i saw a lot of people testifying about his goodness. when i contacted him he gave me hope and send a Herbal medicine to me that i took and it seriously worked for me, am a free person now without problem, my HERPES result came out negative. I pray for you Dr Ero God will give you everlasting life, you shall not die before your time for being a sincere and great men. Am so happy, you can also contact him if you have any problem Email:

  2. Thanks for sharing.I found a lot of interesting information here. A really good post, very thankful and hopeful that you will write many more posts like this one.

  3. Hello Everyone out there,I am here to give my testimony about a Herbalist doctor who helped me . I was infected with HERPES SIMPLEX VIRUS in 2011, i went to many hospitals for cure but there was no solution, so I was thinking how can I get a solution out so that my body can be okay. One day I was in the river side thinking where I can go to get solution. so a lady walked to me telling me why am I so sad and i open up all to her telling her my problem, she told me that she can help me out, she introduce me to a doctor who uses herbal medication to cure HERPES SIMPLEX VIRUS and gave me his email, so i mail him. He told me all the things I need to do and also give me instructions to take, which I followed properly. Before I knew what is happening after two weeks the HERPES SIMPLEX VIRUS that was in my body got vanished . so if you are also heart broken and also need a help, you can also email him at {}
    or whatsapp him number: +2349038382931.

    Contact him today and you will have a testimony...Good luck!

    Dr. OLIHA Also Cures:
    1. HIV/AIDS
    2. HERPES 1/2
    3. CANCER
    4. ALS (Lou Gehrig’s disease)
    5. Hepatitis B
    6. chronic pancreatic
    7. Emphysema
    8. COPD (Chronic Obstructive Pulmonary Disease

  4. I was haven herpes 2 on my private part. I have had them for about 2 and a bit years. I am so scared what my mates are going to says if there should fined out i have herpes on my private part and due to the virus my girlfriend broke up with me. I have been to the Doctors 9 times to get it treated. They all come back. I have been using Tee Tree Oil and Wartner (You freeze them at home) and they seem to be keeping the smaller herpes small but they can't seem to treat the larger ones. They don't get any bigger, but then they can't shrink as much. They get smaller a little part at a time. At least they are getting smaller! As soon as I see a new herpes appearing, then I treat it. At the moment I have been using Tee Tree twice a week and then using Wartner every 2 weeks. I was wondering if there was any other information about how to get rid of it. I am only a teenager and I hate it most when it get pi-chins me to scratch it, it get sweets when scratching it most times! I want to get rid of it so bad! DR.ONOKUN website has been a huge help and has helped me realize a lot more about me and my family of genital herpes! so that was when i switch for natural remedy to see if there could be any help by herbal remedy, i search and i saw a great posts by Sarah devise adebayo ehijactor and shanttel Merritt on about the great herbal doctor that get them rid of there disease infection. and this great herbal doctor was called DR.ONOKUN so that was when i contacted him for my own treatment and he prepared me some herbs which i takes for some couples of days, and i take it as he says before i am to no me and my family was perfectly cure for it and never experience it again. please friends if you have herpes virus and you really wants to get rid of it, please contact this great DR.ONOKUN for herbal treatment and you will get rid of it. EMAIL. 

  5. I'm 40 years old female I tested genital herpes (HSV1-2) positive in 2016. I was having bad outbreaks. EXTREMELY PAINFUL. I have try different kinds of drugs and treatment by the medical doctors all to know was avail. Six months ago I was desperately online searching for a helpful remedies for genital herpes (HSV1-2) cure, which I come across some helpful remedies on how Dr OYAGU have help so many people in curing genital herpes (HSV1-2) with the help of herbal treatment because I too believe there is someone somewhere in the world who can cure herpes completely. At of the past 2 months, however, I've been following his herpes protocol Via or +2348101755322 and it stopped all outbreaks completely! To my greatest surprise I was cured completely by following the protocol of his herbal medicine . Don't be discouraged by the medical doctors. There is a cure for HSV with the help of herbs and roots by a herbalist Dr call Dr OYAGU he is so kind and truthful with his herbal treatment, kindly contact him for more information Via or WhatsApp DR on +2348101755322 or visit his website you will be lucky as I am today

  6. DR OYAGU herbal medicine is a good remedy for herpes simplex virus cure. My name is MIGNON WRIGHT , am from USA,I am here to give my testimony about DR OYAGU who helped me in my life, i want to inform the public how i was cured from (HERPES SIMPLEX VIRUS) by DR OYAGU, i visited different hospital but they gave me list of drugs like Familiar, Zovirax, and Valtrex which is very expensive to treat the symptoms and never cured me. I was browsing through the Internet searching for remedy on HERPES and i saw comment of people talking about how DR OYAGU cured them, when i contacted him he gave me hope and send a Herbal medicine to me that i took and it seriously worked for me, am a free person now without any problem, my HERPES result came out negative, I pray to God to never let me and my family forget you in our life, am now cured permanently, you can also get your self cured my friends if you really need this doctor help, you can reach him on his website ; Email: or via whatsapp +2348101755322

  7. I has suffered for Human papillomavirus HPV) for 2years, I was given some tablets at the hospital but I refused to take it, They said I have to be on it for life so I don't want take a drugs everyday for life. No point in taking medicine everyday when u won't get cure from it and I was advice to seek for natural herbal cure, after some time I found dr onokun is the most trustful herbalist that have herbs to cure wicked symptom's,I emailed dr onokun, for 2weeks been his patient he cured my (HPV) with his herbal. I only used his natural herbs for two weeks it was 100% cure. I'm not (HPV) patient anymore. I'm happy about it i finally got cured out of this mess been in my body for 2years. I also recommend you if you're living with (HPV) or herpes symptoms i also want you to be free contact dr onokun with the email attach to my post. or website or facebook:

  8. Good luck to anyone reading this true life story of mine, I Was Diagnosed With type 2 Herpes Virus Last year, And I Was Looking For Solution To Be Cured Luckily I Saw Testimonies On How Dr OYAGU Cure Herpes Virus I Decided To Contact Dr OYAGU I Contacted Him He Prepared A Herbal Medicine Portion And Sent It To Me, I Started The Herbal Medicine For My Health. He Gave Me Step By Step Instructions On How To Apply It, When I Applied It As Instructed, I Was Cured Of This Deadly Herpes Within 2 weeks, I Am Now Herpes Negative. My Brother And Sister I No That There Are So Many People That Have The Same Herpes Virus Please contact Dr OYAGU To Help You Too, And Help Me To Thank Dr OYAGU For Cure Me, I’m Cured By Dr. OYAGU Herbal Medicine, His Contact or visit his website Or Cell Whatsapp Number +2348101755322 thank you

  9. When someone writes an post he/she retains the plan of a user in his/her brain that how a user can understand it.
    So that’s why this post is perfect. Thanks! 토토

  10. Aw, this was an exceptionally nice post. Finding the
    time and actual effort to create a great article… but what can I
    say… I procrastinate a lot and don’t manage to get anything done. 온라인카지노

  11. I like the valuable information you provide in your articles.
    I’ll bookmark your blog and check again here frequently.
    I am quite sure I will learn lots of new stuff right here!
    Best of luck for the next! 경마사이트

  12. There’s certainly a lot to find out about this topic. I like
    all the points you’ve made. 토토

  13. Appreciate it! An abundance of posts.

    Here's my website : -- 안마


  14. You made such an interesting piece to read, giving every subject enlightenment for us to gain knowledge.
    Thanks for sharing the such information with us to read this. 카지노사이트

  15. This post is disseminating valuable information to people who are most concerned of the following issues being targeted by this site. Many certainly will keep coming back to check out updated posts

  16. From the tons of comments on your articles, I guess I am not the only one having all the enjoyment here keep up the good work.

  17. Decent blog and totally exceptional. You can improve however despite
    everything I say this perfect.Keep striving generally advantageous.

  18. Just admiring your work and wondering how you managed this blog so
    well. It’s so remarkable that I can't afford to not go through this
    valuable information whenever I surf the internet!

  19. I've been looking for photos and articles on this topic over the past few days due to a school assignment, 파워볼사이트 and I'm really happy to find a post with the material I was looking for! I bookmark and will come often! Thanks :D

  20. Very good written information. It will be valuable to anybody who employess it, as well as yours truly :). Keep up the good work – for sure i will check out more posts. Feel free to visit my website; 야설

  21. I'm glad that i found this type of site, after so many hours of searching of a marvelous site like yours so. Thanks a lot. Feel free to visit my website; 한국야동

  22. Pretty good post. I just stumbled upon your blog and wanted to say that I have really enjoyed reading your blog posts. Any way I'll be subscribing to your feed and I hope you post again soon. Big thanks for the useful info. Feel free to visit my website; 국산야동

  23. Seems genuine but rather regardless of whether it's actual it doesn't prevent everybody from fostering their own thoughts of excellence. Thoughts that are persuading, thoughts that are logical and thoughts that are engaging Feel free to visit my website;

  24. Hurrah! Finally I got a weblog from where I be able to actually take valuable facts concerning my study and knowledge. Feel free to visit my website;

  25. Why Suffer With Bad Service Or A Complicated And Expensive System Just To Trade Forex. Check Out Over 25 Highly Rated, Tried-and-tested Brokers. We'll Help You Find The Right One For Your Needs. At Live Forex Trading Our Mission Is To Help You Find The Right Broker So You Can Get On With What Really Matters, Trading. With Our Comprehensive And Transparent Review Of Over 80+ Forex Brokers, You’ll Be Able To Make An Informed Decision That Suits Your Trading Needs.

  26. The Bfarf Stock Overview, keep track of all your favorite stocks in real time across multiple screens, tailored to only show information you need and see as it happens.

  27. What a nice post! I'm so happy to read this. 토토사이트추천 What you wrote was very helpful to me. Thank you. Actually, I run a site similar to you. If you have time, could you visit my site? Please leave your comments after reading what I wrote. If you do so, I will actively reflect your opinion. I think it will be a great help to run my site. Have a good day.

  28. Toto sites, which specialize in Sports Toto Proto, are often old private Toto sites. First-generation Totosites often refer to safety playgrounds that focus on sports betting. 토토사이트 사설토토사이트 안전놀이터

  29. I’m thinking some of my readers might find a bit of this interesting. Do you mind if I post a clip from this and link back? Thanks 사설토토


Add a comment. Registration required because trolls.