Herpesviruses and Other dsDNA Viruses: Overview and Human Infections - Prof. Junjun Liu, Study notes of Virology

Download Herpesviruses and Other dsDNA Viruses: Overview and Human Infections - Prof. Junjun Liu and more Study notes Virology in PDF only on Docsity! Herpesviruses and other dsDNA viruses Introduction • The herpesviruses derive their name from the Greek word herpein, meaning to creep. • >100 herpesviruses have been isolated from a range of hosts including mammals, birds, fish, reptiles, amphibians and molluscs. • Eight of these viruses are human viruses, and most adults in the world are persistently infected with most of them. The human herpesviruses Herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) • Both HSV-1 and HSV-2 infections are lifelong • ~3.7 billion ppl <age 50 (67%) have HSV-1 • ~417 million ppl age 15-49 (11%) have HSV-2 • Initially infect epithelial cells of the oral or genital mucosa, the skin or the cornea. • May enter neurons and may be transported to their nuclei, where they may establish latent infections. Latent infections (a) Virus DNA integrated into a cell chromosome. After infection of the cell the virus genome is integrated into the genome of the host cell, e.g. retroviruses. (b) Virus DNA present as multiple copies of circular molecules. The human herpesviruses Herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) • HSV-1 commonly infects via the lips or the nose between the ages of 6 and 18 months. • A latent infection may be reactivated if, for example, the host becomes stressed or immunosuppressed. • Reactivation results in the production of virions, which in about 20–40 per cent of cases are transported within the neuron to the initial site of infection, where they cause productive infection in epithelial cells, resulting in a cold sore. The human herpesviruses Herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) The majority of genital herpes infections produce either atypical or no symptoms. Only a minority of cases are recognized. The human herpesviruses Varicella-zoster virus • Infection usually occurs in childhood and causes varicella (chickenpox). • It may also spread to nerve cells, where it may establish a latent infection. • Causes shingles Extrachromosomal cicular DNA The human herpesviruses Varicella-zoster virus • After one got chickenpox, the virus remains inactive (becomes dormant) in certain nerves in the body. Shingles occurs after the virus is re-activated in these nerves years later. The human herpesviruses Epstein-Barr virus (EBV) • is transmitted in saliva. • Epithelial cells are infected first then the infection spreads to B cells, the main host cell type for EBV. • Usually, more than 90 per cent of people become infected with EBV during the first years of life, results in few or no symptoms. The human herpesviruses Epstein-Barr virus (EBV) Mononucleosis (Mono) • In developed countries some individuals do not become infected until adolescence or adulthood. • Some adults develop infectious mononucleosis (glandular fever), commonly called ‘the kissing disease’. • EBV is associated with a number of tumors in man The human herpesviruses Human cytomegalovirus • Most infections show no symptoms or mild symptoms. • To a pregnant woman, the virus can infect the placenta and then the fetus, and causes serious consequences. • In the US about 1% of babies are born infected with the virus (about 40 000 per year). • ~7% of these show evidence of virus-induced damage at birth, including small brain size and enlargement of the liver and spleen. • For the other individuals, damage develops at a later stage, such as hearing loss and mental retardation. • Sexually transmitted! The herpesvirus virion relatively complex virions composed of a large number of protein species organized into three distinct structures: • capsid, • Tegument = viral matrix • envelope The herpesvirus virion Genome: linear dsDNA Capsid: icosahedral surrounded by tegument Tegument: also called viral matrix, is a cluster of proteins that lines the space between the envelope and nucleocapsid of all herpesviruses Envelope: contains a large number of spikes The herpesvirus virion • Most of viral structural proteins are commonly named VP (virus protein). • In HSV-1 the most abundant proteins in the capsid and the tegument are VP5 and VP16, respectively. • In the envelope there are at least 12 species of glycoprotein, each of which is prefixed ‘g’, for example gB, gC and gD. HSV-1 replication Entry: • The nucleocapsid and the tegument proteins are released into the cytoplasm • the nucleocapsid then be transported to the nucleus, where virus replication takes place. • The nucleocapsid is rapidly transported along microtubules to the vicinity of a nuclear pore. • The virus DNA is released into the nucleus, where the linear molecule is converted into a covalently closed circular molecule. Transport of HSV-1 DNA and VP16 into the nucleus microtubule NUCLEUS HSV-1 replication tegument proteins : • Are transported to several sites in the cell. • play a variety of roles, including the down-regulation of host DNA, RNA and protein synthesis. • One tegument protein known as virion host shutoff (vhs) protein degrades cell mRNA. • Other tegument proteins are involved in the activation of virus genes. orlgin-binding Bon se" protein —, helicase Genome replication polymerase processivity factor Key: =—_ parental DNA aa5! =a) “' ssDNA-bindIng protein DNA polymerase “+3, Bae primase RNA ae primer seo leading strand | oa -5° heaus polymerase processivity tact RNA DNA goad primer polymerase ca oe noe —> newDNA (arrow indicates synthesis in 3 to 3 direction) Assembly and exit of virions from the cell • dsDNA is packed into procapsid in nucleus • Efficient replication, rolling pol unlimited transcripts Latent herpesvirus infection • Virus RNAs synthesized during latency are known as latency associated transcripts (LATs). • The LATs undergo splicing, and at least one of them plays a role in inhibiting apoptosis, thereby ensuring the survival of the neurone with its latent HSV-1 infection. • the greater the degree to which the host is immunocompromised, the greater the likelihood of reactivation. Family Herpesviridae herpein (Greek) = to creep Hosts: mammals birds cold-blooded animals Diseases: cold sores genital herpes chickenpox/shingles Virion ® Enveloped ® Icosahedral ® 120-200 nm diameter ® Genome: double-stranded DNA 125-240 kbp linear dsDNA transcription (+) MANA Ss genome» ~~ _dSDNA replication