Fundamentals Block 5: DNA Viruses Herpes Viruses

What are the three major parts of the Herpes Virus Structure?

→Linear Double-Stranded DNA
→ Icosahedral Core
→ Envelope

What is the viral infection and replication cycle of a Herpesvirus?

As the herpes virus penetrates into a cell, it sheds its envelope, uncoating and then directing to the nucleus
→ once it enters the nucleus it will break apart its capsid and release its viral DNA
→ proteins are made in the nucleus and the virus is reassembled where it will enter into a vesicle and becomes enveloped in a process known as tegumentation
→ they then egress and exit the cells

What is Establish Latency and how is it related to herpes virus?

Herpes Virus are capable of establishing latency
→ viral genetic material may exist extra chromosomally or get integrated in the host cell DNA becoming a permanent part of the host
→ all Herpes Virus class A viruses establish latency in the nerves

What is the infection progression of someone inflicted by Herpesvirus

Initial infection by the herpesvirus causes acute disease or be asymptomatic where the virus will establish latency
→ reactivation can occur causing recurrent symptoms, new symptoms, or remain asymptomatic
→ some herpes may cause cancer (malignant transformation)

Disease is different depending on whether the patient is immunocompetent (mild or none) or immunocompromised (severe)

What are the viruses in the alpha subfamily in herpes?

HSV-1, HSV-2, and VZV

What are the methods of transmission for HSV-1 and HSV-2

Both HSV-1 and HSV-2 are transmitted through intimate contact with skin and mucosal surfaces
→ HSV-1 is more commonly spread by both anal-genital transmission and oral transmission
→ HSV-2 is by far most commonly spread through anal-genital transmission

What are the clinical manifestations of HSV-1 and HSV-2

While you typically present with oral and mucocutaneous manifestations such as cold sores, other symptoms can be presented
→ the first time a person has the symptoms they are usually worse than recurrent manifestations
→ also cause mucocutaneous infections of the genitals - these are indistinguishable from each other (HSV-1 and HSV-2) and can manifest in place besides your genitals

How can HSV-1 cause ocular infections?

HSV-1 can infect, typically a single eye, causing painful red vision changes that can cause blindness

What is Herpes Encephalitis?

Rare complication from HSV-1 and 2
→ present with altered mental status, personality changes, and seizures
→ has a high morbidity rate

What are the two forms of Neonatal Herpes? How does this occur

occurs during delivery most commonly and is at the greatest risk for transmission if the mom was recently infected/lesions

Localized
→ when a baby comes into contact with a lesion while being pushed out during delivery, causing localized lesions at the area of contact

Disseminated
→ affects multiple organs and can lead to more systemic presentations of the disease

How would you test for viral diseases when the disease is present or the disease is absent?

When the disease is present you would use test such as PCR or antigen testing

When the disease is absent, you would test for the presence of antibodies

What is Varicella Zoster Virus

Class a Herpesvirus spread through the upper respiratory tract where it will replicate in regional lymph nodes
→ replicates in the liver and spleen and then will infect the skin causing vesicular rash
→ causes chickenpox and shingles

What happens following latency of Varicella Zoster Virus?

VZV will travel up the nerve and establish latency in the nerve
→ when reactivated, VZV will cause shingles resulting postherapeutic neuralgia
→ causes a rash associated with a dermatome that typically do not cross the midline
→ shingles causing rashes with specific nerves can cause other complications depending on what tissues they innervate

What are the Beta-subfamily of the Herpes Viruses?

HHV-6 and HCMV
→ Human Herpes Virus 6 and Human Cytomegalovirus

What is HHV-6

Human Herpesvirus-6 which causes Roseola
→ typically presents in children which causes fever and causes rash caused by blanching macules (you can see it but not feel it, and the color goes away when you press down on the skin)

What is Human Cytomegalovirus

Beta Family Herpesvirus that is transmitted through bodily fluids
→ establishes latency in myeloid lineage cells
→ can cause monolike syndromes in children and adolescence
→ CMV can causes issues with the immunocompromised causing severe issues

What can Human Cytomegalovirus cause to immunocompromised patients

Based on the kind of immunocompromised factor can cause different manifestations. For example:
→ Advanced HIV patients will present with Gastrointestinal Disease and Neurologic disease whereas people with bone marrow transplants will have pneumonia

What is the most common viral cause of congenital disease?

Human Cytomegalovirus
→ virus spreads from placenta to fetus which is capable of causing congenital infection

How can you detect Cytomegalovirus Infection

Cytomegalic cell
→ hallmark of infection, an enlarged cell that contains a dense, central owl eye basophilic intranuclear inclusion body

What are the gamma subfamily herpes viruses?

HHV-8 - Karposi-Sarcoma Hepres Virus
HHV-4 - Epstein Barr Virus

What is HHV-4

Epstein-Barr Virus - also known as the “kissing virus” causes infectious mononucleosis
→ may result in lymphoproliferative diseases and cancer
→ enters via the oropharyngeal mucosa via spit
→ establishes latency in B-cells

What are the triad of symptoms associated with infectious mononucleosis

Infectious Mononucleosis caused by HHV-4
→ Fevers
→ Sore Throat
→ Lymphadenopathy (swelling of lymph nodes)

How could you diagnose a HHV-4 patient (2)

People with epstein-barr virus can cause atypical lymphocytes
→ causes very large lymphocytes

Also tested via the Heterophile Antibodies test (Rapid Latex Agglutination Test)
→ take serum from an individual that could have EBV is presented to latex beads with antigen from animals
→ the presence of heterophile antibodies resulting from the clumping of beads will indicate that someone has HHV-4 infection

What is HHV-8?

Kaposi-Sarcoma-Associated Herpesvirus
→ tropic to the B-lymphocytes and causes severe issues in the immunocompromised, especially people with HIV
→ associated with Kaposi Sarcoma, Castleman’s Disease, and Body Cavity Effusion Lymphoma
→ Kaposi Sarcoma are these raised dark papules that appear on the skin