Herpes Virus

herpes viruses general fast facts

large viruses, ds linear DNA, genomes possess terminal and internal repeated sequences, some members can undergo genome rearrangements giving rise to isomers

herpes viruses that commonly infect humans are numbered…

1-8

HHV-1

herpes simplexvirus 1 (HSV1)

HHV-2

herpes simplexvirus 2 (HSV2)

HHV-3

varicella-zoster virus (VZV)

HHV-4

epstein-barr virus (EBV)

HVV-5

cytomegalovirus (CMV)/human cytomegalovirus (HCMV)

HHV-6 (short answer)

human herpes virus 6

HHV-7

human herpes virus 7

HHV-8

kaposi’s sarcoma herpesvirus (KSV/KSHV)

what are properties of HSV1 and 2?

genomes are similar in organization and exhibit substantial sequence homology

can be distinguished by sequence analysis or by restriction enzyme analysis of viral DNA

cross-react serology, but some unique proteins exist for each type

how is HSV1 most commonly transmitted and when are people exposed to it?

saliva, most exposed as children, usually found in oral infections but can cause genital infections if introduced there, can be transmitted during symptomatic and asymptomatic shedding of the virus

how is HSV2 most commonly transmitted and when are people exposed to it?

sexual contact, most exposed when they become sexually active, usually found in genital infections but can cause oral infections if introduced there, can be transmitted during symptomatic and asymptomatic shedding of the virus, risk of transmission to fetus during pregnancy is greater if primary infection occurs close to the time of birth

clinical manifestations of HSV1 or 2 can be due to…

primary infection (first encounter with the virus) or reactivation/recurrent infection (due to activation of the latent virus)

primary infection with HSV1 or 2

2-20 day incubation period depending on infected site and the infecting strain of virus, causes different types of lesions (primary gingivostomatitis, genital herpes, herpetic whitlow, conjunctivitis and keratitis, encephalitis)

primary gingivostomatitis

lesions on the lips and mouth, very common

genital herpes

vesicular eruption of the genitalia, mostly due to HSV2 but up to 1/3 of the cases may be due to HSV1

herpetic whitlow

infection of the fingers, can be acquired by dentists as a result of contamination of the hands by virus-laced saliva or other secretions

conjunctivitis and keratitis

infections involving the eyes, can lead to blindness

encephalitis

either primary or recurrent infection, may lead to permanent defects or death

reactivation/recurrent infection

entails activation of the non-infectious form of the latent virus residing in the neurons of either the trigeminal ganglion or the sacral ganglia, lesions tend to recur at the site of the primary lesion

what can reactivation be provoked by?

menstruation, stress, sunlight (possibly UV rays), local trauma

what is a possible result of HSV reactivation?

bells palsy- facial muscle weakness or paralysis, results from damage to the facial nerve (CN VII)

what is the laboratory diagnosis for HSV1 or 2?

tzanck smear for presumptive diagnosis, syncytia formed from infected cells (but also seen with VZV)

detection of viral antigens in skin scrapings, or specimen which has been inoculated into cell culture

PCR

what is the treatment for HSV1 or 2?

course of primary infection can be altered significantly with drugs like aciclovir and vidarabine, should be administered in early stages of prodromal phase of disease for best results

aciclovir and vidarabine

inhibit viral DNA synthesis

prodromal phase

early stage and symptoms of the condition

how can you prevent HSV1 or 2 infections?

avoid contact with obvious lesions, healthcare workers should wear gloves, avoid sexual contact during outbreaks, use condoms, counseling for HSV-infected pregnant women, prophylaxis to prevent recurrences, wash hands

is there a vaccine for HSV1 or 2?

no

what are the general properties of VZV?

morphologically identical to HSV, no animal reservoir, propagates in cultures of human embryonic tissue and produces typical intranuclear inclusion bodies, causes varicella (chickenpox) and herpes zoster (shingles)

VZV

primarily a disease of older adults and immunocompromised persons, mild in children, incidences increase with advancing age and decrease with degree of immunocompetence, highly contagious in a host not previously exposed to the virus, transmission occurs by direct contact with skin lesions or droplet infection form infectious saliva

varicella (chickenpox)

about 2 week incubation period, a papular rash of the skin and mucous membranes, including the oral mucosa, papules rapidly become vesicular and itchy but painless

zoster (shingles)

occurs primarily as a reactivation of the virus in dorsal root or cranial nerve (usually trigeminal) ganglia, usually affects adults, virus is reactivated despite circulating antibodies, triggered by trauma, drugs, neoplastic disease or immunosuppression

what happens when the trigeminal nerve is affected in shingles?

happens in ~15% of cases, with involvement of the ophthalmic, maxillary, and mandibular divisions, causes severe localized oral pain preceded by rash and can easily be confused with a toothache, involvement of the ophthalmic nerve may lead to eye lesions and sometimes blindness

what are some complications of shingles?

ramsay hunt syndrome- rare manifestation of zoster, vesicular rash on the tympanic membrane and the external auditory canal, together with unilateral facial nerve palsy

postherpetic neuralgia- causes a burning pain in nerves and skin, pain lasts long after the rash and blisters of shingles go away

what is the laboratory diagnosis for VZV?

diagnosis typically made on clinical presentation and patient history, lab tests include tzanck smear, detection of viral antigens, PCR, serology

what is the treatment for VZV?

chickenpox is self limiting and requires symptomatic treatment if any

disseminated zoster in immunocompromised patients requires antiviral drugs which interfere with herpesvirus DNA replication

it is less sensitive to aciclovir than HSV so a higher dose is required, therapy should start within 72 hours of onset

how can you prevent VZV infection?

passive immunization (VZ immune globulin, for people at high risk of severe infection), recombinant zoster vaccine (contains VZV glycoprotein E, prevents shingles in previously infected)

or

live attenuated vaccine (varivax or zostavax)

where is EBV found?

worldwide, more than 90% of adults in US have been infected

how is EBV transmitted?

saliva

infectious mononucleosis (mono)

infection affecting lymph nodes (usually in the neck for EBV), commonly seen in teenagers (peak incidence at 15-20 years old), ‘kissing disease’, monospot test

EBV is heterophile antibody ____ infectious mononucelosis

positive

what other 4 rare but serious diseases is EBV associated with?

oral hairy leukoplakia, burkitt’s lymphoma, nasopharyngeal carcinoma, hodgkin lymphoma

oral hairy leukoplakia

white/cream colored oral lesions, usually on the sides of the tongue, occur in AIDS patients resulting from productive infection of epithelial cells

burkitt’s lymphoma

due to a constitutive expression of myc proto-oncogene resulting from chromosomal translocation in germinal B cells, endemic form is most common with highest incidence in children in equatorial africa and new guinea, also associated with malaria

nasopharyngeal carcinoma

epithelial cell tumor that occurs in adults, rare in the US, highest incidence in southern China including Hong Kong, additional risk factors include high intake of preserved foods, smoking, alcohol use, and genetic predisposition

hodgkin lymphoma

type of B cell lymphoma, pathogenesis is complex

what cell types can CMV productively and latently infect?

lymph nodes (heterophile antibody negative mononucleosis), t-lymphocytes, endothelial vascular tissue, renal epithelial cells, salivary glands

t/f CMV always causes disease

false- rarely causes disease unless other precipitating factors like immunocompromising states

t/f CMV can infect the fetus during pregnancy

true

HHV-6 (long answer)

roseola virus, herpes lymphotropic virus, can cause exanthem subitum (common childhood disorder characterized by mild fever and a facial rash), also called 6th disease

Infectious mononucleosis that is heterophile antibody negative is typically caused by

A. Epstein-Barr virus.

B. Cytomegalovirus.

C. Adenovirus.

D. Parvovirus.

E. Coxsackievirus

B. cytomegalovirus