HHV-6, 7 and 8

Dr. Mazen ZAYLAA

2023-2024
Herpesviruses
• Herpesviruses are an important group of large
(DNA) viruses that includes several important
human viral pathogens.

• The outstanding property of herpesviruses is their

ability to establish lifelong persistent infections
in their hosts and to undergo periodic
reactivation.

• Herpesviruses have been linked with malignant

diseases in humans and lower animals

• Large viruses
• Capsid is icosahedral
• Genome: double stranded DNA.
• Enveloped.

DNA replication and capsid assembly occurs in the

nucleus
HUMAN HERPESVIRUS TYPES 6 AND 7

 HHV-6 and HHV-7, classified as members of the Betaherpesvirinae, have

marked similarities to HCMV in biologic and genome characteristics.

 Both HHV-6 and HHV-7 are causative agents of roseola infantum

(exanthem subitum), although infection with HHV-7 is more frequently
asymptomatic.

 Two variants of HHV-6 have been recognized: HHV-6A and HHV-6B.

 HHV-6B is virtually ubiquitous and is the causative agent of roseola

infantum. HHV-6A has been implicated in the progression of HIV disease
to full-blown AIDS.
Epidemiology and pathogenesis
 Most infections with HHV-6 and HHV-7 occur during the first 3 years of
life, with overall incidence of antibody approaching 90 percent of the
population by age 3.

 Transmission is thought to be via oral secretions because the viruses

replicate in the oropharynx as well as in B and T lymphocytes.

 HHV-7, in particular, is commonly recovered from healthy individuals’

saliva.

 These viruses also infect peripheral blood lymphocytes and the cells of
various solid organs.

 HHV-6A infection of lymphoid cells induces a number of significant cell

responses, including the synthesis of CD4 glycoprotein, interferon- Alpha,
tumor necrosis factor- Alpha, and interleukin-1- Beta.
Epidemiology and pathogenesis
 The ability of HHV-6A to induce expression of CD4
in cells not normally expressing it extends the range
of cells that can be infected by HIV.

 In addition, HHV-6A transactivates transcription of

HIV, accelerating the rate of cell death in coinfected
cells.

 Latently infected cells are found among the peripheral

blood lymphocyte population.

 HHV-6A was shown to accelerate AIDS progression

in an animal model of the disease.
Clinical significance

 HHV-6 infections resulting in disease are

most common in infants and individuals
who are immunocompromised.

 Primary infections: Symptomatic roseola

infantum occurs in roughly one third to one
half of infants with a primary HHV-6
infection.

 It is characterized by a high fever of 3 to 5

days’ duration, after which a characteristic
erythematous macular rash appears on the
neck and trunk, resolving after several more
days without sequelae.

 HHV-7 infection has been shown to produce

an identical clinical picture.
Clinical significance

 Of greater clinical significance is that

primary HHV-6 infection of infants is
the cause of many acute febrile
illnesses and febrile seizures in the
absence of the characteristic rash.

 In some of these cases, HHV-7 has

been shown to be the causative agent,
whereas, in others, the patient was
coinfected with both HHV-6 and
HHV-7. no rash

 Over 20 percent of emergency room

visits for febrile illness in infants and
one third of febrile seizures are
caused by primary infection with
HHV-6 and/or HHV-7.
Clinical significance
 Recurrent infections: Following immunosuppression for
organ transplantation or immunocompromise related to
HIV infection reactivation of latent HHV-6, frequently
together with HCMV, has been associated with sometimes-
fatal interstitial pneumonitis, ever, hepatitis, and
encephalitis as well as with transplant rejection.
 Three factors may accelerate the progression from early
HIV infection to terminal AIDS:

1) HHV-6A broadens the range of cell types infected by HIV

by inducing CD4,
2) Coinfected cells are killed more rapidly,
3) Extensively disseminated HHV-6A infection frequently
occurs in terminal AIDS patients. The most common
clinical syndrome associated with HHV-6 in AIDS patients
is encephalitis.

HHV-6 has also been associated with multiple sclerosis,

Alzheimer disease, and chronic fatigue syndromeHHV-6 has
also been associated with multiple sclerosis, Alzheimer disease,
and chronic fatigue syndrome
Laboratory identification
 A simple diagnostic test for primary infection with HHV-6 or HHV-7 is not
available.

 PCR amplification has been used to demonstrate HHV-6 DNA in the CSF
of patients with neurologic disease and in the serum of patients undergoing
posttransplant reactivation of a latent infection.
Treatment and prevention
 Because of its genetic relationship to HCMV, HHV-6 is generally inhibited
by the same drugs (ganciclovir, cidofovir, and foscarnet), but extensive
clinical trials have not yet been done.

 In AIDS patients, treatment of the HIV infection appears to reduce the

amount of HHV-6 as well.

 Foscarnet for HHV-6 encephalitis. Roseola goes away on its own and is
treated supportively.

 No vaccine is currently available for these viruses.

 HUMAN HERPESVIRUS 8
(KAPOSI SARCOMA–ASSOCIATED HERPESVIRUS)

 KSHV is lymphotropic ( B cells appear to be the primary

target for longterm viral latency ).

 The virus also infects a limited number of endothelial cells,

monocytes, epithelial and sensory nerve cells.

 KSHV is not as ubiquitous as other herpesviruses. It is more

prevalent in certain geographic areas (Italy, Greece, Africa)
and in patients with AIDS.

 The KSHV genome contains numerous genes related to

cellular regulatory genes involved in cell proliferation,
apoptosis, and host responses that presumably contribute to
viral pathogenesis
 HUMAN HERPESVIRUS 8
(KAPOSI SARCOMA–ASSOCIATED HERPESVIRUS)

 Is the cause of Kaposi sarcomas.

 Contact with oral secretions

 Sexually, vertically, by blood, and through organ transplants.
 Viral DNA has also been detected in breast milk samples in Africa

 Is involved in the pathogenesis of:

❖ Body cavity-based lymphomas occurring in AIDS patients

❖ Multicentric Castleman disease HHV-8 DNA sequences were discovered in

biopsy specimens through the use of PCR analysis

 Primary Effusion Lymphoma: HHV-8 can also infect B cells and cause
B cell lymphoma
KAPOSI SARCOMA
 Vascular tumor of skin, lymph
nodes and visceral organs.

 Occurs in AIDS patients.

 Kaposi sarcoma is the most

common cancer in sub-
Saharan Africa
Laboratory identification
 Detection of Viral DNA in patient
specimens using PCR assays.

 Direct virus culture is difficult and

impractical.

 Serologic assays are available to measure

persistent antibody to KSHV ( indirect IF,
Western blot, ELISA).
Treatment
 Foscarnet, famciclovir, ganciclovir, and cidofovir have
activity against KSHV replication.

 The level of KSHV replication and rate of new Kaposi

sarcomas are markedly reduced in HIV-positive patients on
effective antiretroviral therapy, probably reflecting
reconstituted immune surveillance against KSHV-infected
cell