Scientists estimate that about two-thirds of the human population is infected with at
least one herpes simplex virus.
For the most part, these viruses present as cold sores around the lips or mouth, or blisters
on the genitals.
According to a study conducted in 2014 by scientists at the University of California,
San Diego School of Medicine, these viruses have been co-evolving with humans and even
the ancestors of modern humans for millions of years.
Let’s dig into what they’re all about.
Herpes Simplex Viruses fall into the group of human herpesviruses, which are large, enveloped
viruses that contain double-stranded DNA.
The DNA-based core of these viruses is surrounded by an icosahedral capsid structure.
We know that capsids, in general, are assembled from individual proteins that gather together
in an organized structure to protect the genetic material of the virus.
In an icosahedral capsid structure, proteins gather into an approximation of a sphere;
but made up of many symmetrical subunits.
In the case of human herpesviruses, they take this a step further.
The DNA core of human herpesviruses is surrounded by an icosadeltahedron structure.
It sounds complicated, but it’s actually pretty easy to picture if you’ve ever seen
a soccer ball.
A soccer ball is an icosadeltahedron.
Ok, so let’s keep going.
This soccer ball-shaped capsid is then enclosed by an envelope that contains glycoproteins.
In human herpesviruses, these glycoproteins help the virus attach to their host, fuse
with the host membrane, and escape control by the host immune system.
The space between the envelope and the capsid is called the tegument.
This space holds viral enzymes and proteins that help kickstart the process of replication
once inside a host cell.
With all of these parts, it makes sense that human herpesviruses are on the larger side
as far as viruses go, typically spanning about 150 nanometers in diameter.
However, like other viruses that contain an envelope, human herpesviruses are sensitive
to solvents, acid, detergents, and drying.
Now that we’ve familiarized ourselves with human herpesviruses in general, we can get
more specific.
Herpes Simplex Viruses, or HSV, were the first in their group to be recognized.
The name “herpes” comes from a Greek word meaning “to creep.”
There are two types of Herpes Simplex Viruses: HSV-1 and HSV-2.
They share very similar characteristics, like DNA homology, antigenic features, symptoms,
and tissue tropisms.
However, there are some subtle but significant differences that set them apart.
Let’s think about the genetic makeup of HSVs in particular.
The double-stranded DNA genome of HSVs encodes somewhere around 80 proteins.
About half of these are involved with creating more copies of itself in the way of replication,
meaning things like a DNA-dependent DNA polymerase.
The other half control how the virus interacts with the host cells and the host’s immune
response, so at least 10 glycoproteins that serve as viral attachment proteins.
Unfortunately for us, HSV can infect most types of human cells, and even cells of other species.
However, we should note that although HSV can infect other animal cells, HSV infection
is exclusively a human disease.
Once the virus has attached to a cell, it penetrates the host cell by fusing its envelope
with the cell surface membrane.
Once the virus has fused with the host cell, it releases its capsid into the cytoplasm
of the host cell, along with some enzymes that help the virus make more copies of itself.
Now, HSV has evolved a very sophisticated and step-wise system to replicate itself.
The first things created are what we call the immediate early gene products.
This includes DNA-binding proteins, which help stimulate DNA synthesis and transcription.
Next up are the early proteins, which include catalytic proteins like DNA-dependent DNA
polymerase, to kickstart DNA replication.
Replication of the viral genome then triggers transcription of genes that encode structural
proteins and other necessary proteins for viral function.
From here, the virus is assembled piece by piece before being released either by exocytosis
or cell lysis.
In the case of neurons, when compared to other types of infected cells, the virus may either
replicate immediately, or establish latency, depending on which viral genes are expressed.
Thinking about the mechanism of infection for HSV-1 and HSV-2, they’re actually quite
similar.
Both viruses initiate infection through mucosal membranes or breaks in the skin, they replicate
in the cells, they cause disease at the site of infection, and establish latent infection
within neurons.
However, there are some differences.
HSV-1 infection most commonly occurs above the waist, while HSV-2 infection most commonly
occurs below the waist.
However, both types can infect both above and below the waist.
Additionally, there are some differences in growth characteristics, and HSV-2 has a greater
potential to cause viremia, which means viruses in the blood, and systemic symptoms.
HSV has evolved complicated mechanisms to escape the immune system, as well.
When it comes to latent infection, things like stress, trauma, sunlight, or fever can
trigger a recurrence, causing the virus to replicate within a nerve cell all over again.
Interestingly, latency and recurrence can vary a good bit between people.
For example, some people may never experience symptoms during recurrence, but can still
spread the virus to others.
Now, let’s talk more about how HSV-1 and HSV-2 are transmitted.
HSV-1 is typically spread by oral contact, like kissing, or through sharing toothbrushes,
glasses, or other saliva-contaminated items.
However, let’s keep in mind that the virus itself is actually quite fragile outside of
a cell, so there’s really a short window where you could potentially catch the virus
by sharing a drink.
In addition it can enter through a break in the skin.
HSV-1 infection is also incredibly common.
HSV-2, on the other hand, is spread mainly by sexual contact or from an infected mother
to her infant at birth.
Some common symptoms of HSV infection are cold sores and fever blisters, often at the
corners of the mouth or next to the lips.
When it comes to genital herpes, about 90% of cases are caused by HSV-2, while the other
10% are caused by HSV-1.
It’s worth noting that it is possible for HSV-1 or HSV-2 to cause serious disease, either
in immunocompromised people, or by infecting tissues like the eyes or brain.
There are multiple tests that are fairly quick to diagnose HSV-1 and HSV-2 infection.
By now, scientists have developed multiple drugs to treat HSV infection, like FDA-approved
acyclovir, abbreviated as ACV.
While there isn’t a vaccine available for HSV just yet, there are vaccines being developed
to either prevent transmission or treat infected people.
And now that we’ve covered HSV, let’s move on to a few more human herpesvirus diseases
you might have heard of.