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Describe the four types of infection and how the virus production manifests over time.

acute infection - fast peak and then destruction of virus

persistent infection - constant presence of virus before death

latent, reactivating infection - virus peaks up at various times in life accompanied by an immune response

slow virus infection - virus infects certain cells and lays dormant until a later time period where it explodes and causes death


herpesvirus family

eight different herpesviruses isolated from humans

classified into three subfamilies based on biological properties and genomic analyses

certain genes are conserved among members of all three subfamilies

depending on the particular virus and the population studied, infection rates are generally between 60-90%


Name the eight different herpesviruses isolated from humans.

HSV-1, HSV-2, HCMV (human cytomegalovirus), VZV (varicella-zoster virus), EBV (Epstein-Barr virus), HHV6, HHV7, and KSHV (Kaposi's sarcoma associated herpesvirus)

HHV6 has recently been split into HHV6a and HHV6b


human alpha--herpesviruses

neurotropic, characterized by a broad host range and are highly litic in cell culture

short reproduction cycles

includes HHV1, HHV2, and HHV3 (VZV)



restricted host range and grow more slowly in culture

cells infected with beta subfamily members often display an enlarged cytoplasm, referred to as cytomegaly

members include cytomegalovirus, HHV6, and HHV7



lymphotropic and can be oncogenic

severe diseases arises from latency

members include Epstein-Barr virus and Kaposi's sarcoma associated herpes virus


genes conserved among members of all three subfamilies

genes for structural proteins and enzyme enzymes for DNA replication


hallmarks of all herpesvirus infections

the ability of the virus to establish latent infections during the primary encounter with the host and to reactivate to cause secondary disease long after recovery from primary disease


three classes of herpesviruses

class I - herpesviridae (mammals, reptiles, birds)

class II - alloherpesviridae (amphibians, fish)

class III - (malacoherpesviridae, bivalves)



route of entry - exposure of broken skin or mucosa to oral or genital secretions

primary disease - gingivostomatis, pharyngotonsilitis, keratitis, encephalitis (rarely)

principle site of latency - neurons of sensory or autonomic ganglia

reactivation disease - cold sores/fever blisters (herpes labialis), keratitis, encephalitis (rarely)

above the waist

leading cause of blindness in the developed world



route of entry - exposure of broken skin or mucosa to oral or genital secretions

primary disease - meningitis, disseminated disease

principle site of latency - neurons of sensory or autonomic ganglia

reactivation disease - recurrent mucocutaneous lesions (genital sores)

below the waise



route of entry - respiratory

primary disease - chicken pox

principle site of latency - neurons of sensory ganglia

reactivation disease - zoster

causes systemic primary disease instead of localized disease

cutaneous lesions in the outer layers of the stratified squamous epithelium produces infectious virus that can spread through air

incubation and acute illness

live attenuated vaccine for general use


receptors required for HSV viral entry

nectin-1 - a cell adhesion molecule expressed in epithelial cells and neurons

HVEM - a member of the TNF receptor family expressed in leukocytes and epithelial cells

PILRalpha - a co-receptor also required for virus entry and may simultaneously trigger the cell to be more permissive to the subsequent infection


HSV latency

virus enters the endings of adjacent neurons and transports within axons to the sensory ganglia

viral DNA is injected into the nuclei after viral particles arrive at the neural somas

latent infection of neurons is characterized by the absence of viral gene expression except for the latenct-associated transcript (LAT)


latency-associated transcript (LAT)

encodes a stable intron that accumulates in the nuclei of latently infected neurons and microRNAs that interfere with teh TGF-beta pathway

protects latently infected neurons from apoptosis



treatment of choice for life-threatening HSV infection

can be used prophylactically to reduce the frequency and severity of recurrent lesions


HSV severe disease

sporadic encephalitis


neonatal herpes


sporadic encephalitis


no strong predispositions

most often involves temporal lobe

highly fatal

permanent neural damage in survivors

CNS latency allows for recurrence

presentation is similar to stroke an may include confusion, reduction in consciousness, difficulty speaking, change in personality, and seizures



leading cause of infectious blindness in USA

corneal scarification and neovascularisation are conesquences of the immune response


neonatal herpes

mostly HSV-2

predominantly spread during birth

infection can also be in utero or postnatally

1 in 1,200-2,000

three forms include:

localized mucocutaneous disease


disseminated disease


primary (natural host)

species that maintains virus in nature

typically experiences relatively benign recurrent infections resulting from successful establishment of latency


secondary (dead-end host)

virus causes a typically fatal encephalitis


Herpes B

herpes virus that usually infects resus macac monkeys

very severe for humans, goes straight to the brain and kills the person


describe the structure of herpesvirus.

core, capsid, tegument, and envelope


herpes core

viral DNA ranging from 120-240 kbp

double-stranded linear DNAs

tightly packaged inside capsid under high pressure


herpes capsid

125 nm diameter icosahedron with 162 capsomers

composed predominantly of 4 viral proteins

encases viral DNA

visible as a multi-faceted ball in the center of the image, and the capsomers are the very small shapes composing the capsid surface


herpes tegument

viral proteins located between the capsid surface and the envelope

these proteins do not make a structure that is easily visible with a standard electron microscope


herpes envelope

lipid bilayer containing about a dozen viral membrane proteins and glycoproteins

some glycoproteins can be seen as spikes emanating from the lipid envelope


herpesvirus infectious cycle

virus attaches to cell surface receptors and fuses with the cell membrane

capsid transported to the nucleus via microtubules

viral genome injected into th enucleus through pores

tegument proteins transported to the nucleus, direct cell RNA polymerase to transcribe immediate-early (IE) viral genes

IE mRNAs encode viral regulatory proteins that induce the expression of early (E) and late (L) genes

E mRNAs encode enzymes required for viral DNA replication

viral DNA is replicated, providing template for L gene expression and progeny viral genomes for packaging

capsids assemble in the nucleus, where viral DNA genomes are packaged into the performed capsids

capsids acquire temprary envelop by budding through the inner nuclea rmembrane



herpes virus tegument protein

virion host shutoff, interferes with cellular protein synthesis

prevents cells from calling out for help or warning other cells