Herpesviridae

Tiny germs can live in our bodies.

They can hide for a long time. Some germs make us feel sick. Most adults have had one.

These germs can stay very quiet inside us. They hide inside our cells. This helps them stay for a long time.

Sometimes, the germs wake up. When they wake up, they make more germs. This can make a person feel sick.

These germs live in many animals too. They can be in birds and fish. They can even be in reptiles.

It is amazing how these tiny germs work.

Herpesviruses are a big family of tiny germs. These germs are viruses. They carry DNA, which are the instructions they use to work.

Most adults have had at least one kind. These viruses can live in many animals too. You can find them in birds, fish, and reptiles. Some live in pigs or cows.

Each virus has a special shape. A single virus is called a virion. It has a protein cage called a capsid. This cage holds the DNA. Around the cage is a layer called the tegument. The whole thing is wrapped in an outer skin called an envelope. This envelope has tiny spikes on it. These spikes help the virus stick to a cell.

These viruses are very good at hiding. They can stay in a quiet state called latency. This means they stay in your cells without making you sick. They can stay this way for a long time. Sometimes, the virus wakes up. This is called reactivation. When it wakes up, it makes many new viruses. This can make a person feel sick with a fever or a rash.

Herpesviruses are a huge family of tiny germs called DNA viruses. They are very important to study because they cause many different diseases in animals and humans. The family name comes from a Greek word that means "to creep." This describes how some of these viruses cause skin sores or blisters to spread.

Scientists have found more than 100 different types of these viruses. Some can make people feel sick right away. Others can hide inside a person for a very long time without causing any trouble.

Every herpesvirus has a specific way of working inside a living cell. The whole virus particle is called a virion. It starts by using tiny spikes on its outer skin to stick to a cell. Once it attaches, the virus enters the cell and breaks apart. This allows the viral DNA to travel into the cell's nucleus. The nucleus is the control center where the virus begins to make copies of itself.

This process uses the cell's own tools to build new viruses.

Scientists have been studying these viruses for a long time. In 1971, a group called the ICTV named "Herpesvirus" as a specific group. At that time, they only knew about 23 different viruses in this family. Since then, our knowledge has grown a lot. We now know that these viruses have been around for millions of years. They actually grew and changed alongside the animals they infect.

This is called coevolution, where the virus and the host change together.

There are many different types of herpesviruses to learn about. Nine types primarily infect humans, and many are very common. For example, herpes simplex 1 and 2 are well known. Varicella zoster is the virus that causes chickenpox and shingles. More than 90% of adults have been infected with at least one type. In the United States, about 15% of adults aged 35 to 72 have had them.

Other types live in birds, fish, reptiles, and even pigs.

These viruses are experts at staying in the body through a state called latency. This is like a long sleep where the virus stays quiet. The body tries to hide the viral DNA by wrapping it up tightly. If the body's defenses stay strong, the virus stays dormant and does not make you sick. However, sometimes the virus can wake up, which is called reactivation. This can happen if a person is under a lot of stress. When it wakes up, it can cause a fever or a rash.

The Herpesviridae family consists of a large group of DNA viruses. These viruses infect many different animals, including humans. They are significant because they can cause a wide range of diseases. The name comes from the Greek word *herpein*, which means "to creep." This refers to how certain infections cause skin lesions or blisters to spread across the body.

Each individual virus particle is called a virion. Every virion shares a common, complex structure. At the center is a double-stranded, linear DNA genome. This genome contains between 100 and 200 genes. This DNA is protected by an icosahedral protein cage called a capsid. The capsid is made of 161 parts called capsomers. These include 150 hexons and 11 pentons. A portal complex on the capsid allows DNA to enter and exit. Surrounding the capsid is the tegument. The tegument is an amorphous layer containing 26 different proteins. These proteins help transport the capsid to the nucleus and activate gene transcription. The entire structure is wrapped in a lipid bilayer membrane called an envelope. This envelope has glycoprotein spikes protruding from it. Without these spikes, a virion is about 186 nm in diameter. With the spikes, it can reach 225 nm.

Herpesviruses follow a specific life cycle inside a host cell. The process begins when a virion contacts a cell. The viral envelope glycoproteins bind to specific receptors on the cell surface. Once bound, the virion is internalized and dismantled. This allows the viral DNA to migrate into the cell nucleus. Inside the nucleus, the virus performs DNA replication and gene transcription. The virus can exist in two different states: lytic or latent. During a lytic infection, the virus actively replicates and often causes cell death. During latency, the virus remains quiet and does not cause immediate illness. This allows the virus to persist in the host indefinitely.

Latency is a sophisticated way for the virus to hide. When a virus enters a cell, the immune system tries to protect the host. The cell responds by wrapping the viral DNA around proteins called histones. This condenses the DNA into chromatin, which makes the virus dormant. In this state, the virus produces latency-associated transcripts, or LATs. However, if the chromatin is loosely bundled, the DNA remains accessible. If the virus reactivates, it transitions from LATs to lytic genes. This reactivation can be triggered by cellular stressors like hypoxia or interrupted protein synthesis. In animal models, local trauma and systemic stress can also induce reactivation. Lytic activation often results in symptoms like fever, headache, and rash.

Scientists categorize these viruses into three main subfamilies. The first is Alphaherpesvirinae, which includes genera like Simplexvirus and Varicellovirus. The second is Betaherpesvirinae, which contains the Cytomegalovirus genus. The third is Gammaherpesvirinae, which includes the Lymphocryptovirus genus. These subfamilies are divided into seventeen different genera. For example, the Alpha subfamily includes viruses that infect birds, sea turtles, and mammals. The Beta subfamily includes viruses that infect humans, monkeys, and rodents. The Gamma subfamily includes viruses that infect humans and various mammals.

Human infections are extremely common across the globe. Nine specific herpesvirus types primarily infect humans. At least five of these are widespread among most human populations. Herpes simplex 1 and 2 (HSV-1 and HSV-2) can cause oral or genital herpes. Varicella zoster virus (VZV) causes chickenpox and shingles. Epstein-Barr virus (EBV) is linked to mononucleosis and certain cancers. Human cytomegalovirus (HCMV) is another major human pathogen. More than 90% of adults have been infected with at least one of these types. In the United States, as many as 15% of adults aged 35 to 72 have been infected. Other human types include HHV-6A, HHV-6B, HHV-7, and HHV-8.

Evolutionary studies show that these viruses are very old. The three mammalian subfamilies likely arose between 180 and 220 million years ago. These viruses have undergone a process called coevolution with their hosts. This means the viruses and their hosts changed together over time. Many sublineages were likely created before the mammalian radiation 80 to 60 million years ago. Some genera, such as Iltovirus, are estimated to be 200 million years old. Other genera, like Mardivirus, appeared between 150 and 100 million years ago. This long history explains why they are so successful at staying in host populations.

Herpesviruses are also experts at immune evasion. They use special proteins to trick the host's immune system. For example, cytomegalovirus encodes a protein called cmvIL-10. This protein mimics a human protein called interleukin 10. It helps the virus inhibit the synthesis of pro-inflammatory cytokines. This process involves the phosphorylation of the Stat3 protein. Specifically, the protein PI3K phosphorylates Stat3 at the S727 residue. This action helps the virus suppress the cell-mediated immune response. By doing this, the virus can avoid being destroyed by the body's natural defenses.