Apr 19, 2016//
Roughly 80 percent of the U.S. population is infected with the herpes virus. While the virus is very easy to get, it remains dormant in many people, who never even know they have it. This is partly because it effectively evades the immune system, taking up refuge in the central nervous system.
Dr. Greg Smith is a herpes expert. He is a professor in the microbiology-immunology department at Northwestern University’s Feinberg School of Medicine. After obtaining his Ph.D. from the University of Pennsylvania, Smith did a post-doc at Princeton University.
His research on herpes looks at novel targets for antivirals and engineering recombinant viral particles as effective gene delivery vehicles.
In this episode, Smith talks with STEM-Talk host Dawn Kernagis about his educational and research path to becoming a herpes expert. He also touches on polio as an example of an earlier virus that was largely defeated, and how that was different than herpes. Finally, Smith touches on the development of viral vectors and vaccines to win against the more severe forms of herpes that some people are genetically predisposed to get.
For a list of Smith’s publications, check out his bio page at web site of Northwestern University: http://tinyurl.com/jl6jsam
:47: Smith’s lab studies the molecular mechanisms that propagate and are responsible for the spreading of Herpes.
2:47: Ken Ford reads 5-star iTunes review of STEM-Talk, from “I prefer DOS IHMC”: ‘Fantastic lineup and well-assembled, informative conversations on fascinating topics. Keep ‘em coming.”
4:18: Smith’s interest in research began in elementary school, when his father bought him an Apple II computer for Christmas—and told him to program his own games. Programming “really helped me think in a logical, progressive way,” Smith said.
5:46: In college, Smith discovered that “molecular biology was a way to get at the programming that underlies life.”
6:12: In graduate school, Smith studied microbes, which he describes as “essentially the best human biologists; if you study them, you are studying yourself.”
7:56: Smith was not interested in viruses initially because they seemed like simple entities. He didn’t want to study just one protein.
8:56: Smith worked with Lynn Enquist at Princeton University, a “bacteriologist-big thinker,” Smith says, who got him thinking: “How do larger, more complex viruses get into our nervous system? That got me started on the path that I’m still on today.”
9:16: Viruses are extremely diverse entities in biology; they are more diverse than the rest of life put together. Any organism is infected by many viruses, which are “small nanomachines that are genetically derived.”
10:43: Smith describes what a virus looks like: a shell made up of a thin layer of protein.
12:00: Smith wanted to study something with a lot of diversity/complexity. With that comes very interesting biology. All viruses have two things in mind: They want to make more copies of themselves, and they want to disseminate those copies all over place. Herpes, because of its larger genetic content and physical size, allows it to do a lot of interesting things to achieve those goals.
13:00: Polio is a small neuro-invasive virus. You ingest it and it replicates in your gut. It can get into your blood, and nerves/spinal chord. This can cause polio myelitis, which was rampant in the 1950s.
14:18: Herpes is evolved to get into nervous system. That is how it survives. It’s extremely good at it.
15:00: Most people know about herpes simplex virus type 1, or HSV-1, which causes cold sores. But it actually goes into the central nerve system (CNS) and sets up shop. It does not express proteins, so essentially lies dormant there. “The immune system doesn’t know it’s there. So now you’ve got it there for the rest of your life.”
17:25: Commercial break: STEM-Talk is an educational service of the Florida Institute for Human and Machine Cognition, a not-for-profit research lab pioneering ground-breaking technologies aimed at leveraging human cognition, perception, locomotion and resilience.
18:28: Smith answers the question about how the herpes virus gets into the CNS: “The answer here is two-fold: From the virus side, what kind of machinery evolved to allow to achieve that end? From our side, our body’s side, how is it we are protecting our nervous system so that things like this don’t usually happen?”
18:56: Ninety-nine times out of a hundred, our bodies are pretty good at keeping polio at bay. Most people would only get an upset stomach from polio. Most viruses are low-frequency, sporadic things.
20:25: The herpes virus has figured out how to get around all of these barriers—reliably and efficiently.
22:04: The herpes virus has evolved with a big capacity to travel long distances within the body. Smith describes it as “walking from L.A. to New York in a straight line…it travels a very long distance down the nerve fiber to find a neuron deep inside your head.”
23:04: Basically a herpes virus is like a marathon runner. It can’t get lost or stop along the way.
26:52: The best outcome for the virus is for it to effectively go to sleep, so your immune system won’t see that it’s there; and won’t try to remove it. Then it’s established, and you’re carrying it for life.
28:58: Bacteria in our gut is being infected by other viruses, called phages. The complexity of the biology of all this is really astounding, when you look at the bigger picture.
29:19: Dawn comments: “We’re not just human. We seem to be these walking ecosystems.”
29:25: The microbiome would be “one of biggest organs in our body,” Smith said.
30:03: Some people argue that herpes should not be considered pathogenic; but symbiotic. “Nowhere near that many people experience cold sores.” Most people infected don’t exhibit symptomology. But it does replicate in the neurons. “Is this really a pathogen because it doesn’t cause disease most of the time?”
31:56: Chicken pox is also a neuro-invasive herpes virus.
33:11: Herpes simplex virus type I is leading cause of infectious blindness in the U.S. and developing world. On occasion, it will spread from the peripheral nervous system into the central nervous system, and when it does that, the outcome/prognosis is very poor.
34:36: Cold sores are the most common disease manifestation of herpes that you can get. Other complications include: the virus transmitting into the eye and causing loss of vision. Or in the brain, causing encephalitis.
35:34: Herpes type 2 causes genital lesions, which are contagious like cold sores. If a mother giving birth has an active infection, she can transmit the virus to the child, who doesn’t have a developed immune system. C-sections minimize the risk of transmitting the infection.
38:39: Whether or not a person expresses the virus may depend on the genetic background of an individual. You might have a deficiency that doesn’t allow you to mount a good immune response to certain conditions.
39:40: Smith mentions work of Jean-Laurent Casanova at Rockefeller University in New York, who is heading a large project with contributions from several groups. Their research is on children in whom the virus has gone to the brain, which is the most severe form of the infection. Deficient in both copies of gene, so they can’t make the Toll-like receptor-3 protein at all.
43:52: Casanova found that the kids who were deficient in TLR3 were otherwise healthy, which makes some think that the TLR-3 mechanism might have co-evolved with herpes to protect us.
45:00: It turns out the family tree of viruses is consistent with the family tree of mammals. Every species has its own variants of these viruses.
46:07: We are not gong to win this battle by nature alone. Our bodies are not going to develop a way to protect us from the herpes virus. There is no evolutionary path to that end. The viruses are all moving faster than we are.
49:52: Developing viral vectors to deliver genetic information that is beneficial is one long-term application of these studies. And coming up with vaccines.
51:09: If you can make the virus replicate out at the body’s surface, and never get into the nervous system, your immune system will attack and adapt, but the virus won’t be able to hide in the CNS.
52:42: “Reactivation” in the herpes virus can be caused by stress; for example, virus-associated cold sores often show up during times of stress.
55:50: The science of all this is really from the collective enterprise of the researchers. Annually we meet on this specific topic. This is where initial breakthroughs occur…. Where you start putting these puzzle pieces together.
57:53: These viruses will produce these particles, which transmit the virus from cell to cell or person to person. These particles make up a complex machine. It touches a cell, something is triggered, and you get a series of events.
59:40: We’re just starting to understand the nanomachine machine. Every time we understand something, it’s like a wow moment.
1:00:08: Dawn thanks Smith.
1:00:35: Ford caps the interview: “Herpes must be among the more amazing infections; its ability to move about, evade the immune system, and survive in a quiescent but persistent form seems remarkable—and frankly, somewhat worrisome.”