Monday, March 13, 2017

Hantavirus Life Cycle and Infection Process

A viruses are only alive, metabolizing energy and reproducing, when they is comfortably at home. That would not be a bad thing, but virus homes are inside the cells of their host species, or any other species where they find good accommodations. Humans play host to the family of virus that causes the common cold. The mouse equivalent of the common cold appears to be hantavirus. 

Amazing image of a bacteriophage virus from an unknown source. NOT a hantavirus.

Viruses may be the most completely stripped down and simple, living things that we know of. They are so stripped down that a virus, in and of itself, wouldn’t be called alive by most biologists. To be alive it would need some kind of metabolism, an energy handling system, and it would need to be able to reproduce itself. By themselves, the parts of a virus can’t do much of anything. No metabolism, no production of new virus parts, and no new viruses.

But like other living things, viruses exist in different forms in different phases in their existence. Viruses are very much alive, having both a metabolism and the ability to reproduce themselves when they are inside the cells of a suitable, more complex creature, like a plant or an animal.

To make more viruses, they have to take over the biochemistry system of a living cell and force it to make more viruses. The intruder must coopt the cell’s energy and resources to first manufacture parts of the virus, then to assemble those parts into new viruses and expel them into the environment so they can find new cells to attack and infect.

An article that describes this amazing process for a different class of viruses, the bacteriophage, which attack bacteria, can be found at the link below (free access). These viruses resemble tiny spaceships, or eyedropper syringes that attach to a cell wall, drive a needle through it, and inject the DNA into the cell for takeover. 

Bacteriophage virion diagram and models. (from reference below)

Bacteriophage SEM image and diagram. (from source above)

Bacteriophage viruses are quite different from hantavirus, which has a much simpler, almost spherical structure. I'm showing these diagrams and micrographs of a bacteriophage to give an idea of the elegance, of the natural nano-technology at play in a virus' ability to infection and manipulate cells. 

Fortunately, those cells are not just waiting to be attacked, the target of infection, the would-be host, will mount an immune response every bit as sophisticated as the viral assault. 

A typical virus is something like a million times smaller than the cell it will attack, so to overcome the immune responses,  a virus needs to “know” what it is doing. It needs to know what to expect, in a biochemical sense, both outside, and inside of that target cell. For this reason, a virus can’t just attack any cells in any other species. Also, in part for that reason, when a virus makes the jump from a host species where it exists like the common cold, causing little damage, to another, only roughly related species, it can wreak havoc in the target species' body.

Viruses evolve alongside, inside, actually, of their host species until they have adapted to that organism so completely that they are perfectly attuned cell-pirates. For Sin Nombre hantavirus, that perfect soul-mate match is the deer mouse. Other strains of hanta have apparently evolved together with other, closely related rodents, such as the White Footed mouse and the New York virus, a close relative of Sin Nombre.    
White Footed mouse, carrier of the New York virus.
When a virus is active, it is duplicating its RNA or DNA, producing the components of the capsule and coat, and otherwise exploiting the cell’s resources to do its own bidding. Once this process is complete, many copies of the portable virus form are produced and assembled and ready for release from the cell

This other form of a virus is called a virion, which ought to be a common word, but it isn’t. A virion is like a virus seed. When you see a picture of a “virus” what it really is a picture of is the virion of that virus. You wouldn’t call a pumpkin seed a pumpkin, or a pumpkin plant. It is only the DNA information that codes for a pumpkin plant, enclosed in a special shell that protects it, nourishes it, and interacts with the soil to germinate and grow.

Virions are comprised of either DNA, or RNA, either nucleic acid chain type can form viruses, that code for all the virus parts, and the rest of the equipment that genetic material needs to invade a cell and take over its metabolism.
Transmission electron micrograph of hantavirus virions. 
CDC/ Cynthia Goldsmith
The virion is the final virus thing in portable form, the infective device, whose parts are created and assembled by the mechanisms in a cell that has been taken over. These new virions are then expelled from the cell and somehow circulated to a new host. That may be another cell in the same creature, the most common thing. Or passage into urine, feces, or other shedding debris from a virus carrier, and then on to another victim.

Transmission electron micrograph of hantavirus virions.
CDC/ Cynthia Goldsmith
The structure of the hantavirus virions is important, not just to the virus but to us, because that affects how they are transported into humans, and how the immune system fights back against it.

Hantavirus virions are roughly spherical, a little less than 1/5 of one micron in diameter, less than 1/100,000 of an inch. They are nowhere near as large as pollen grains, for instance. The finest pollen grain is around 30 times the diameter, and thousands of times as massive as a hantavirus virion. These virus particles make dust look like boulders.

The outside of the virion is made of a spherical protein envelope that surrounds the RNA that encodes for the hantavirus genes. These genes make the pieces that comprise the virion, the RNA itself, and the proteins that make the “capsule” or “capsid.”

On the surface of the capsid are an array of other proteins that help the virus attach to and penetrate the cell wall its future host. These proteins are what typically triggers immune responses that are the bodies’ main defense against hanta.  

This capsule does a lot more than carry an RNA pill. It contains the chemical/structural information that is needed to break into and enter mouse cells, and yours.

The fact that these virions are nearly spheres means that they can flow and move relatively well compared with more complicated shapes. Another famous virus, called bacteriophage T-6, has a far more complex shape than hantaviruses. T-6 is shaped like a miniature spaceship, or a hypodermic from hell, that attaches itself to a bacteri a cell wall, drives a hollow needle through the cell wall, and then compresses the gene-carrying component and injects the DNA into the cell, taking over its machinery to reproduce more virus.
Transmission electron micrograph of mouse feces with hantavirus visions.
CDC/ Cynthia Goldsmith
Hantaviruses are a genus of viruses within the larger virus family called the bunyaviruses or, even more sinisterly, the bunyaviridae. Most of the other viruses in the bunyaviridae family that cause disease in humans are transmitted to us by arthropod vectors – mosquitos, ticks, lice and others. These carriers of the viruses are called vectors because they only convey the viruses that were produced in some other species. A mosquito bites someone with a viral infection and draws blood, then bites another person and delivers the virus to them.

The virus is being carried by the mosquito, and may be adapted to remain intact within it, but it isn’t taking over the mosquito’s cells to reproduce itself. That task is left to the natural “host species” that the virus has evolved with, and adapted to. When it is in a vector species, it is, at least for the most part, in a passive, virion state.

A virus that has evolved while living in humans for many generations is likely to be well-adapted to working with human anatomy. In this case, the virus probably has a good chance of achieving a new infection in another human with only a small number of virions, or a low concentration of virus. So even though the amount of virus discharged into a human by a mosquito is likely small, it can transmit diseases that are well adapted to their new human host.

Hantavirus, however, is transmitted to humans from a host species, the species that the virus has evolved with. Differences and similarities in hantavirus genes closely match the differences and similarities in their host species. A hantavirus that is endemic to deer mice is likely to be very similar to a hanta that is endemic to the closely-related white footed mouse, another “New World” mouse. Both of those hantaviruses are likely to be dissimilar to those that have evolved alongside an Old World rodent species.

When hantavirus invades a human, it is in an environment that it is only partly prepared for. This is probably the reason that it appears to take a significant number of hantavirus virions for infection to occur. It is also likely the reason that the disease causes so much damage to the human organism. Both factors will be discussed more fully in an upcoming post.

Now, of course, we are living in an ever-smaller world, and all of those species are involved in a planet-wide mixing pot of pathogens and people. We will examine some of the challenges that mixing and evolving process is bringing in the field of "emerging pathogens," the sometimes new, sometimes ancient pathogenic species that are continually changing threats to us all.


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