Herpes virus

Home » Microbiology and Infectious Disease » Microbiology and Infectious Disease thread session guides » Herpes virus
Headshot of Joanna Breems, MD, FACP · Clinical Assistant Professor
Joanna Breems
MD, FACP · Clinical Assistant Professor
envelope icon phone icon
Table of Contents
High-yield summary

  Overview of Herpesviruses (HHV 1–8)

Virus

Common Name

Latency Site

Key Diseases

HHV-1

HSV-1

Trigeminal ganglia

Oral herpes, encephalitis

HHV-2

HSV-2

Sacral ganglia

Genital herpes, neonatal HSV

HHV-3

VZV

Dorsal root ganglia

Chickenpox, shingles

HHV-4

EBV

B cells

Mono, Burkitt lymphoma, NPC

HHV-5

CMV

Monocytes

Mono-like illness, congenital CMV

HHV-6/7

Roseolovirus

T cells

Roseola (exanthem subitum)

HHV-8

KSHV

B cells

Kaposi sarcoma

 

 Pathogenesis and latency

  • Latency: Viral genome persists without active replication.

  • Reactivation triggers: Stress, immunosuppression, fever, sunlight.

  • Immune evasion: Downregulation of MHC I, latency-associated transcripts (LATs), infection of immune-privileged sites (e.g., neurons).

 

  Diagnosis

  • PCR: Gold standard for HSV, VZV, CMV.

  • Tzanck smear: Multinucleated giant cells (low sensitivity).

  • Monospot (heterophile Ab): EBV.

  • Serology: VCA, EA, EBNA for EBV; CMV IgM/IgG for CMV.

  

  Clinical pearls by virus

  • HSV-1/2

    • Primary: Painful vesicles, gingivostomatitis (HSV-1), genital ulcers (HSV-2).

    • Reactivation: Cold sores, genital lesions.

    • Complications: HSV-1 → encephalitis (temporal lobe), HSV-2 → aseptic meningitis.

    • Neonatal HSV: Skin, CNS, disseminated disease.

  • VZV

    • Primary: Chickenpox—vesicles in different stages, centripetal spread.

    • Reactivation: Shingles—dermatomal, painful vesicles.

    • Complications: Post-herpetic neuralgia, zoster ophthalmicus (V1), Ramsay Hunt (CN VII/VIII).

  • EBV

    • Mono triad: Fever, pharyngitis, lymphadenopathy.

    • Atypical lymphocytes: Reactive CD8+ T cells.

    • Complications: Splenic rupture, Burkitt lymphoma (t(8;14)), nasopharyngeal carcinoma, oral hairy leukoplakia (AIDS).

  • CMV

    • Mono-like illness: No pharyngitis or heterophile Abs.

    • Congenital CMV: Sensorineural hearing loss, periventricular calcifications.

    • Immunocompromised: Retinitis, colitis, pneumonitis.

  • HHV-8

    • Kaposi Sarcoma: Vascular tumor in AIDS.

    • Other: Primary Effusion Lymphoma, Multicentric Castleman Disease.

   

  Treatment and prevention

Virus

First-line treatment

Notes

HSV/VZV

Acyclovir, Valacyclovir

Requires viral thymidine kinase

CMV

Ganciclovir, Valganciclovir

Foscarnet/Cidofovir for resistance

EBV

Supportive only

Avoid ampicillin → rash

HHV-8

HAART, chemo

For KS in HIV/AIDS

  • Vaccines:

    • VZV: Varivax (live attenuated), Shingrix (recombinant).

    • No vaccines for HSV, EBV, CMV, HHV-8.

 

  Step 1 high-yield tips

  • HSV-1 = most common cause of sporadic encephalitis in the United States.

  • Temporal lobe involvement on MRI = think HSV encephalitis.

  • Tzanck smear = multinucleated giant cells (but doesn’t differentiate HSV from VZV).

  • EBV: Avoid contact sports (splenic rupture risk).

  • CMV: Most common congenital viral infection.

  • HHV-8: Think AIDS patient + vascular tumor = Kaposi Sarcoma.

 

Learning goals

  1. Name the various herpes group viruses (1-8) and identify the most common clinical presentation for each, including risk factors and features from history and physical examination
  2. Correlate the pathogenesis of acute, latent, and reactivation stages for herpes simplex virus (HSV) and varicella-zoster virus (VZV) and describe the clinical manifestations and possible complications of each stage for HSV and VZV
  3. Compare and contrast the epidemiology, clinical presentation, and laboratory findings for the mononucleosis syndrome caused by Epstein-Barr virus (EBV) versus cytomegalovirus (CMV)
  4. Explain the role of therapeutic and preventative measures in herpes virus infections

Required pre-class materials

These are not required; they are supplementary to the large-group session. They are intended as a curated guide to content focused on the learning objectives. There are both textbook and video resources for this session for students to use per their preference. For each reference, I have designated the learning goal addressed with a learning goal icon and and number.

Click the  blue icons below to go to the resources listed.

  •  Section on Herpes Viruses
    This chapter is organized similarly to Sherris, but a bit more condensed/brief.

1
Table 37-3. Important features of common herpesvirus infections

Virus Primary infection Usual site of latency Recurrent infection Route of transmission
HSV-1 Gingivostomatitis1 Cranial sensory ganglia Herpes labialis,2,3 encephalitis, keratitis Via respiratory secretions and saliva
HSV-2 Herpes genitalis, perinatal disseminated disease Lumbar or sacral sensory ganglia Herpes genitalis2,3 Sexual contact, perinatal infection
VZV Varicella Cranial or thoracic sensory ganglia Zoster2 Via respiratory secretions
EBV Infectious mononucleosis1 B lymphocytes Asymptomatic shedding3,4 Via respiratory secretions and saliva
CMV Congenital infection (in utero), mononucleosis1 Monocytes Asymptomatic shedding2 Intrauterine infection, transfusions, sexual contact, via secretions (e.g., saliva and urine)
HHV-85 Uncertain6 Uncertain Kaposi’s sarcoma Sexual or organ transplantation

CMV = cytomegalovirus; EBV = Epstein–Barr virus; HHV-8 = human herpesvirus 8; HSV = herpes simplex virus; VZV = varicella-zoster virus.

1Primary infection is often asymptomatic.

2In immunocompromised patients, dissemination of virus can cause life-threatening disease.

3Asymptomatic shedding also occurs.

4Latent EBV infection predisposes to B-cell lymphomas.

5Also known as Kaposi’s sarcoma–associated herpesvirus.

6A mononucleosis-like syndrome has been described. Kaposi’s sarcoma itself also can result from a primary infection.

  •  This is a detailed review of herpes viruses. Focus on clinical aspects/disease section of each of the herpes viruses.
    Focus on chapter introduction/overview box and study the “key points” in blue text/blue boxes online.

  • SketchyMicro

    Useful mnemonics for classic organism associations that USMLE and boards like to test .

Viruses:

    • 3.1. Herpes simplex virus type 1 and 2 (dendritic keratitis; 11 min)
    • 3.2. Epstein-Barr virus (13 min)
    • 3.3. Cytomegalovirus (12 min)
    • 3.4. Varicella-zoster virus (12 min)

Videos

RWJF has video playlists for HSV, VZV, and EBV. Content is summarized here to better direct your use. Highest-yield videos for this session’s objectives are marked with

  • RWJF videos
    HSV II (10:08)

    2 Clinical manifestations of HSV with comparison of HSV 1 & 2. Includes brief descriptions of clinical manifestations of cutaneous, ocular, CNS infection and considerations in the immunocompromised host.

  • RWJF videos
    HSV III (9:00)

    4 Diagnostic approach, role of antiviral therapy for different clinical manifestations and for different hosts, and strategies to prevent HSV.

  • RWJF videos
    EBV Diagnostics (11:00)

    3 Uses and limitations of heterophile antibody. A good summary of use of antibodies in viral infections in general and a summary of the EBV-specific antibodies that are used in diagnostics. EBV serologies can be difficult to interpret, at this point, it is worth having awareness of the different antibodies and that a combination is used to establish presence of and type of infection.

  • RWJF videos
    EBV Manifestations (9:00)

    Review of clinical findings in Burkitt Lymphoma, Nasopharyngeal Carcinoma, Hodgkin Lymphoma, CNS Lymphoma, Post-transplant lymphoproliferative disease, Oral hairy leukoplakia. These are all important entities, and common associations that USMLE has an inclination to test. Lymphoma is covered in more detail within Heme-Onc component. CNS lymphoma and OHL will be briefly revisited when we cover HIV/AIDS.

  • RWJF videos
    HSV I (9:00)

    Basic virology of HSV including classification, viral structure, mechanism of viral entry, mechanism of viral replication, pathogenesis of HSV infection, and basic HSV epidemiology.

  • RWJF videos
    HSV IV (10:00)

    Neonatal HSV and vertically transmitted infections. While an important clinical manifestation of HSV, this topic will be re-visited in reproductive health module of the curriculum.

  • RWJF videos
    HHV6 and HHV 7 (9:00)

    Interesting and detailed description of the virology of HHV6 & 7. Clinical considerations in the usual cases (children) and less common, but serious, infection in immunocompromised persons.

  • RWJF videos
    EBV Viral Latency (7:30min)

    Interesting and very succinct summary of virologic dynamics and pathogenesis of latency with EBV and its connection to the lymphoproliferative diseases associated with EBV.