Herpesviridae

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.