Herpes Virus Introduction

Herpesviridae is the name of a family of enveloped, double-stranded DNA viruses with relatively large complex
genomes. They replicate in the nucleus of a wide range of vertebrate hosts, including eight varieties isolated in
humans, several each in horses, cattle, mice, pigs, chickens, turtles, lizards, fish, and even in some invertebrates,
such as oysters. Human herpesvirus infections are endemic and sexual contact is a significant method of
transmission for several including both herpes simplex virus 1 and 2 (HSV-1, HSV-2), also human
cytomegalovirus (HHV-5) and likely Karposi's sarcoma herpesvirus (HHV-8).

In total, there are 8 herpesvirus types that infect humans: herpes simplex viruses 1 and 2, varicella-zoster virus, EBV
(Epstein-Barr virus), human cytomegalovirus, human herpesvirus 6, human herpesvirus 7, and Kaposi's sarcomaassociated herpesvirus.
At least five species of Herpesviridae HSV-1 and HSV-2 (both of which can cause orolabial herpes and genital
herpes), Varicella zoster virus(which causes chicken-pox and shingles), Epstein-Barr virus (which
causes mononucleosis), and Cytomegalovirus are extremely widespread among humans.

The increasing prevalence of genetial herpes and corresponding rise of neonatal infection and the implication of
Epstein-Barr virus (HHV-4) and Karposi's sarcoma herpesvirus as cofactors in human cancers create an urgency
for a better understanding of this complex, and highly successful virus family.
Virion Structure
All herpesvirus virions have four structural elements.

Core. The core consists of a single linear molecule of dsDNA in the form of a torus.

Capsid. Surrounding the core is an icosahedral capsid with a 100 nm diameter

constructed of 162 capsomeres.

Tegument. Between the capsid and envelope is an amorphous, sometimes asymmetrical,

feature named the tegument. It consists of viral enzymes, some of which are needed to
take control of the cell's chemical processes and subvert them to virion production, some
of which defend against the host cell's immediate responses, and others for which the
function is not yet understood.

Envelope. The envelope is the outer layer of the virion and is composed of altered host
membrane and a dozen unique viral glycoproteins. They appear in electron micrographs
as short spikes embedded in the envelope.

Genome Characteristics
Herpesvirus genomes range in length from 120 to 230 kbp with base composition from 31% to
75% G+C content and contain 60 to 120 genes. Because replication takes place inside the
nucleus, herpesviruses can use both the host's transcription machinery and DNA repair enzymes
to support a large genome with complex arrays of genes. Herpesvirus genes, like the genes of
their eukaryotic hosts, are not arranged in operons and in most cases have individual promoters.
However, unlike eukaryotic genes, very few herpesvirus genes are spliced.
The genes are characterized as either essential or dispensable for growth in cell culture. Essential

genes regulate transcription and are needed to construct the virion. Dispensable genes for the
most part function to enhance the cellular environment for virus production, to defend the virus
from the host immune system and to promote cell to cell spread. The large numbers of
dispensable genes are in reality required for a productive in vivo infection. It is only in the
restricted environment of laboratory cell cultures that they are dispensable.
All herpesvirus genomes contain lengthy terminal repeats both direct and inverted. There are six
terminal repeat arrangements and understanding how these repeats function in viral success is an
interesting part of current research.
Biological Properties
Four biological properties characterize members of the Herpesviridae family.

Herpesviruses express a large number of enzymes involved in metabolism of nucleic acid

(e.g. thymidine kinase), DNA synthesis (e.g. DNA helicase/primase) and processing of
proteins (e.g. protein kinase).

The synthesis of viral genomes and assembly of capsids occurs in the nucleus.

Productive viral infection is accompanied by inevitable cell destruction.

Herpesviruses are able to establish and maintain a latent state in their host and reactivate
following cellular stress. Latency involves stable maintanence of the viral genome in the
nucleus with limited expression of a small subset of viral genes.

Strategies for Success

The success of herpesvirus infections depends upon several strategies. The first is the fast
efficient way the virion invades the host cell, turning off host protein synthesis and releasing
viral DNA into the nucleus, where replication and virion production start immediately. Another
strategy that herpesviruses share is the ability to thwart attacks from the host. Tactics include
inhibiting splicing of mRNA, blocking presentation of antigenic peptides on the cell surface and
blocking the apoptosis (cell death) induced by viral gene expression. A third important strategy
shared by herpesviruses is their ability to hide their bare, circularized genome in the nucleus of
lymphoma and central nervous system cells and then return to productive infection months, even
years later. These latent herpesvirus infections are often benign, but can be devastating to
newborns and immuno-suppressed individuals.
Herpesviridae Subfamilies
Alphaherpesvirinae. Members of this subfamily are neurotropic (infect nervous system
tissue), have a short reproductive cycle (~18 hr.) with efficient cell destruction and variable
host range. The human Alphaherpesvirinae with their commom name, scientific name and the
disease they cause are:
Herpes simplex virus 1

Human herpesvirus 1

facial, labial and ocular lesions

Herpes simplex virus 2

Human herpesvirus 2

genital lesions

Varicella-zoster virus

Human herpesvirus 3

chickenpox and shingles

Betaherpesvirinae. Members are lymphotropic, have a long reproductive cycle, restricted host
range and infected cells become enlarged (cytomegalo). Human Betaherpesvirinae include:
Human cytomegalovirus

Human herpesvirus 5

infectious mononucleosis

(no common names)

Human herpesvirus 6 & 7

mild early childhood roseola

Gammaherpesvirinae. These herpesviruses are also lymphotropic and specific for either T or
B lymphocytes. Members of this subfamily isolated in humans are:
Epstein-Barr virus

Human
herpesvirus 4

cofactor in human cancers

Karposi's sarcoma
herpesvirus

Human
herpesvirus 8

cofactor in Karposi's sarcoma which was extremely

rare until the advent of AIDS.