Herpes Simplex and Varicella-Zoster Virus

Herpesviridae

• Herpesviridae constitutes a large family of DNA viruses
• These viruses cause infections and certain diseases in animals and humans
• Members of this family are commonly known as herpesviruses
• Herpesviruses cause both latent and lytic infections
• Herpesviridae virion consists of envelope proteins, outer and inner tegument, nucleocapsid, major capsid protein, triplex, and portal vertex

Herpes Viruses - Properties

• Herpes viruses are enveloped, double-stranded DNA viruses
• The family contains six significant human pathogens
• All herpes viruses are structurally similar, having an icosahedral core surrounded by a lipoprotein envelope
• Herpes viruses are known for causing latent infections
• In latent infections, the initial acute disease is followed by an asymptomatic period
• During the asymptomatic period, the virus remains in a quiescent (latent) state
• Symptoms of subsequent episodes are similar, but others like varicella zoster virus are different

Classification of Herpes Viruses

• Herpes simplex virus 1 & 2 and varicella virus cause vesicular rash within primary infection and reactivation
• Primary infection is often more severe than reactivation
• Cytomegalovirus and Epstein-Barr virus do not result in a vesicular rash
• The herpes virus family is divided into three categories based on the type of cell most infected and the site of latency: alpha, beta, and gamma herpes virus

Herpes Virus Subfamilies

• Alphaherpesviruses include HSV-1, HSV-2, and VZV
• Betaherpesviruses include CMV, HHV-6, and HHV-7
• Gammaherpesviruses include EBV and HHV-8
• Latent or persistent infection is set up following primary infection
• Reactivation is more likely during periods of immunosuppression
• Both primary infection and reactivation are more serious in immunocompromised patients

Family Herpesviridae Overview

• There are at least 25 viruses in this family
• Currently, herpesviridae is divided into three subfamilies
• Eight or more herpes virus types are known to frequently infect humans
• These include Herpes simplex type 1 (HSV-1, HHV-1) and type 2 (HSV-2, HHV-2)
• Other viruses include Varicella-zoster virus (VZV, HHV-3), Epstein-Barr virus (EBV, HHV-4)
• Also note Cytomegalovirus (CMV, HHV-5), Human herpes virus 6 (HHV-6), Human herpes virus 7 (HHV-7), and Human herpesvirus-8 (HHV-8)

Properties of Herpes Viruses

• Herpes simplex-1 (HSV-1) is in sub-family Alphaherpesvirinae and it infects Mucoepithelia cells
• It has a latency in Neurons and is transmitted through Close Contact
• Herpes Simplex-2 (HSV-2) is in sub-family Alphaherpesvirinae and infects Mucoepithelia cells
• It has a latency in Neurons and is transmitted through Close Contact, usually sexually
• Varicella Zoster virus (VSV) is in sub-family Alphaherpesvirinae, infecting Mucoepithelia cells
• It has a latency in Neurons and is transmitted through Contact or respiratory route
• Epstein-Barr virus (EBV) is in Gammaherpesvirinae and infects B lymphocyte, epithelia cells
• Latency also happens in B lymphocytes
• Cyomegalovirus (CMV) is in Betaherpesvirinae
• Affects Epithelia, monocytes, and lymphocytes
• Latency in Monocytes, lymphocytes and possibly others is a transmission point for Contact, blood transfusions, transplantation, congenital issues
• Herpes lymphotropic virus is in Betaherpesvirinae, and affects T lymphocytes and others
• Latency in T lymphocytes and others, with contact transmission through respiratory route
• Human herpes virus-7 (HHV-7) is in Betaherpesvirinae- T lymphocytes and others
• Latency is in T lymphocytes and others and has Unknown transmission type
• Human herpes virus-8 is in Gammaherpesvirinae, and affect Endolethial cells
• It has Unknown latency, and Exchange of body fluids transmission

Herpes Simplex Viruses (HSV) Properties

• Herpes simplex viruses belong to the alphaherpesvirus subfamily of herpesviruses
• These viruses are enveloped with double-stranded DNA, possessing a genome size of around 150 kb
• The genomes of HSV-1 and HSV-2 share 50-70% homology
• There is also antigenic cross-reaction with VZV
• Humans are the only natural host for HSV

HHV1 (HSV1) Key Points

• Human Herpes virus 1 (HHV1), also known as herpes simplex virus 1 (HSV1), causes cold sores around the mouth
• It can lead to infection in the genital area
• HHV1 is usually contagious and spreads through skin-to-skin contact or mucous membranes
• It may be spread through sharing eating utensils, razors, and towels

HHV2- HSV2

• Human herpes virus 2 (HHV2) causes genital herpes
• Typically transmitted through sexual contact, making this a sexually transmitted infection
• HHV2 can also cause cold sores in the facial area
• HHV2 infection is contagious and spreads through skin-to-skin contact

HSV Symptoms

• Symptoms of HSV start anywhere from 2 to 20 days and may last for several weeks
• The symptoms include outbreak of pain, itching blisters on/near external sexual organs/lips
• Vaginal discharge, fever and headache, muscle aches and fatigue
• Painful urination and swollen lymph nodes are other symptoms

HSV Pathogenesis

• During the primary infection, HSV spreads locally, leading to a short-lived viremia, where the virus is disseminated in the body, spreading to the craniospinal ganglia
• The virus establishes latency in the craniospinal ganglia
• The mechanism of latency is unknown; there may be no viral replication (true latency)
• OR there is some viral persistence which means low-level replication
• Reactivation is triggered by factors like stress and infection
• Reactivation can also be triggered by pneumococcal and meningococcal infection, fever, irradiation, sunlight, and menstruation

Diagnosis of Herpes Simplex Virus

• Diagnosis involves laboratory culture
• Tests to use: DNA tests and PCR testing
• A swab can be taken from an active lesion
• Colour-coded antibodies determine whether the source is HSV-1 or HSV-2
• Electron microscopy used to ID fluids from blisters

Herpes Simplex Management

• Antiviral chemotherapy is indicated in cases of severe primary infection, dissemination, sight is threatened, and there is a herpes simplex encephalitis
• Measures to avoid genital herpes: Barrier methods of contraception e.g. condoms, avoid having intercourse with infected person, avoid oral sex

Reducing Pain and Treating Herpes Simplex

• Relief measures: soaking affected area in salt, pain killers
• Herpes simplex is not curable because of ability to stay dormant in cells for long period
• Treatment available for acute outbreaks using Acyclovir
• This reduces the viral reproduction in the initial outbreaks with Valaclovir and Famcyclovir
• Antibiotic ointments may be applied to prevent secondary bacterial infection

Varicella-Zoster Virus (VZV)

• Human herpes virus 3 (HHV 3) also called varicella-zoster virus (VZV)
• VZV causes chickenpox or varicella and may also cause a recurrent virus infection of the skin called shingles or herpes zoster

VZV Properties

• VZV is an enveloped, double-stranded DNA virus belonging to the alphaherpesvirus subfamily of herpesviruses
• The genome size is 125 kbp, featuring long and short fragments with a total of 4 isometric forms

VZV Epidemiology

• Primary varicella as an endemic disease
• Commonly occurs in childhood
• Highest prevalence in the 4-10 year old age group
• Varicella is highly communicable; attack rate of 90% in close contacts
• Most people are infected before adulthood, but 10% of young adults remain susceptible

VZV Pathogenesis

• The virus gets in via the respiratory tract and spreads to the lymphoid system
• After an incubation period of 14 days, the virus arrives at target organ skin
• Following the primary infection, the virus remains latent in the cerebral or posterior root ganglia
• In 10-20% of individuals, a recurrent infection occurs after several decades
• The virus reactivates in the ganglion and tracks down the sensory nerve to the area of the skin innervated by the nerve, producing a varicellaform rash in the distribution of a dermatome

Varicella Symptoms

• Primary infection causes varicella or chickenpox
• Incubation period is 14-21 days
• Presence of a fever, lymphadenopathy, and a widespread vesicular rash
• Diagnosed the virus on presentation of symptoms
• Complications are rare, but are mores frequent and severe in adults and immunocompromised patients

Complications of Varicella

• Secondary bacterial infection of the vesicles
• Life-threatening complications include viral pneumonia, encephalitis, and hemorrhagic chickenpox

Varicella Symptoms and Signs

• Include development of small itchy groups of blisters on the skin
• Starts from the face, scalp, or chest which and quickly spreads throughout the body
• Usually appears a few days after infection- Blister dries out after 4-5 days and create with scabs
• Then falls off 9-13 days later- This is often preceded or accompanied by: fever/fatigue/headache/flu-like symptoms

Prevention of Varicella

• Vaccine is called Varivax
• It is given to every child over 1 year old, followed by a second dose being given to a person over 13
• If you've never had chickenpox, avoid contact to the infected patient to avoid spreading to others

Herpes Zoster (Shingles)

• Mainly affects a single dermatome of the skin
• Can occur at any age, however mainly occurs in patients over the age of 50
• The latent virus reactivates in a sensory ganglion and tracks down the sensory nerve to the appropriate segment
• A characteristic eruption of vesicles in the dermatome is often accompanied by intense pain that may last for months (postherpetic neuralgia)

Additional Issues of Herpes Zoster

• Herpes zoster affecting the eye and face may cause great issues
• As with varicella, herpes zoster is issue in immunocompromised patients
• This can lead to reactivation, developing earlier in life meaning increased complications
• Potential Rare complications: encephalitis and disseminated herpes zoster

Symptoms of Herpes Zoster

• Include itching, tingling or even severe pain
• A rash that begins as redness followed by blisters
• Herpes zoster Usually covers only one side of the body
• Rash follows along nerve where the virus was dormant.
• In most patients, the rash is located on their trunk.
• The face is the next common location, potentially involving tongue, eye, or ear.
• Can also result in swollen lymph nodes and upset stomach

Herpes Zoster: Laboratory Diagnosis

• In most instances clinical evidence is enough for varicella/zoster diagnosis
• Testing is seldom required
• Virus isolation is rarely carried out due to length of incubation period
• Direct detection includes and uses an electron microscope used for vesicle fluids
• Cannot distinguish between HPV and VZV
• immunofluorescence determines differences with skin scrappings
• Serology test determines VZV IgG presence, indicating past infection of primary infection

Herpes Zoster: Management

• Acyclovir treatment is required for immunocompromised person
• Is not a cause of concern healthy individual
• Biggest challenge is management of postherpetic neuralgia
• Antiviral therapy is recommended for all patients over 50 years presenting with herpes zoster
• Three drugs can treat herpes zoster: acyclovir, valicyclovir, and famciclovir
• Use calamine or hydrocortisone lotion to reduce symptoms
• Preventative measures for those contracting severe varicella/leukaemia/pregnant women

Epstein-Barr Virus (EBV)

• Human herpes virus 4 (HHV 4)
• A major cause of Mononucleosis
• Is a very contagious disease
• Nucleocapsid size has a 100 nm diameter
• There are 162 capsomeres

Epstein-Barr Virus (EBV) - Properties

• EBV belongs to the gammaherpesvirus subfamily of herpesviruses
• The nucleocapsid size is 100 nm in diameter
• It has 162 capsomers
• Its membrane is derived by budding of immature particles through the cell membrane and is required for infectivity
• The genome is a linear, double-stranded DNA molecule with 172 kbp
• Viral genome typically doesn't incorporate into cellular DNA; it forms circular episomes residing in the nucleus
• Despite having a genome encoding 100-200 proteins, only a select few have been identified

Epstein-Barr Virus (EBV) - Pathogenesis

• Infection leads to a lifelong carrier state, with the immune system keeping low-grade infection in check
• Epithelial cells in the pharynx of seropositive individuals shed viral replication
• EBV can immortalize B-lymphocytes in vitro and in vivo
• EBV-immortalized B-cells are found in circulation; continually cleared by immune surveillance

Diseases Associated with EBV

• Infectious mononucleosis
• Burkitt's lymphoma
• Nasopharyngeal carcinoma
• Lympho-proliferative disease and lymphoma in the immunosuppressed
• X-linked lymphoproliferative syndrome
• Chronic infectious mononucleosis
• Oral leukoplakia in AIDS patients
• Chronic interstitial pneumonitis in AIDS patients

Immunocompromised Patients and EBV

• Primary infection: EBV causes latency, reactivation may occur when immunity is impaired
• EBV causes lymphoproliferative lesions/lymphoma
• Transplant recipients: renal transplant, EBV associated with the development of lymphoproliferative issues.
• AIDS patients: EBV associated with the development of oral leukoplakia of lymphoma
• Ducan X-linked lymphoproliferative: for males inheriting a defective gene in
• X-chromosome of cell tissue

EBV Diagnosis

• Acute infection is tested with a antibody test
• Cases of Burkitt's lymphoma diagnosed histologically, stained with antibodies to lambda light chains to reveal a monoclonal tumor, with origin in the B-cell
• Can be expressed to assess IgM at cell surface
• Cases of NPC should be diagnosed histologically
• The determination of the titre of anti-EBV VCA IgA screening for early lesions and monitoring treatment

EBV Vaccination

• Controlled with BL and NPC for primary EBV infections
• Can be given Early in lifespan- Used useful in seronegative organ transplants and severe IM, such as male spring of X-linked syndrome carriers
• It should not be preferable for subunit vaccine w/dangers that lives viruses still contain tumorigenic properties
• Development Antigen chosen for antigens neutralizing

CMV: Cytomegalovirus Properties

• CMV belongs to the betaherpesvirus subfamily of herpesviruses
• The CMV genome structure is similar to other herpesviruses
• It consists of long and short segments which may be orientated in either direction, giving four isomers
• It is a double-stranded, DNA enveloped
• The nucleocapsid is 105nm in diameter with 162 capsomers

Cytomegalovirus Epidemiology

• CMV may be transmitted vertically and horizontally with little effect on host
• Transmission may occur in utero, prenatally, and postnatally
• Once infected: carries virus for life; activates from time to time
• Infectious virions appear in urine and/or in saliva
• Reactivation can also be vertically transmitted
• People with primary infection can be re-infected without differing from reactivation
• Higher infected are higher in developing (90%), v. developed (70%)

CMV Pathogenesis

• The virus remains dormant for the rest of the person's life
• Is very easily reactive
• Can be spread in utero/perinatally/postnatally
• Perinatal infection-is acquired sexually
• In infected organ and breast-milk
• Postnal infection- is saliva/sexual products

Cytomegalovirus: Clinical Presentations

• Congenital infection: cytomegalic inclusion disease
• Perinatal: asymptomatic
• Post natal: asymptomatic, in minority infectious mononucleosis is developed (fever, lymphadeopathy)
• Immunocompromised can develop severe CMV disease as (pneomitis/ etitisis/ocolitics)

How CMV is Transmitted

• Direct contact with body fluids- and blood
• Transmitted by infected organs
• Can be sexually active
• And pregnancy to the fetus

CMV Symptoms

• Infants affected after they are born may develop hearing/ mental issues/ retarded development
• Some may develop pneumonia, hepatitis
• Others may create mono/ fatigue

CMV: Prevention

• Standard hygiene - Pregnant women can take steps
• Precautions in Health: Prevent transmission between the patients and staff

CMV Diagnosis

• Can be conducted through a lab test
• PCR, Viral culture CMV, and throat swab
• Serologic determines the CMV

CMV: treatment: prevention

• Transplant recipients
• Disease is difficult with measures
• Matching and and screening CMV
• Negative blood

HHV 6 and 7:

• Belong to the betaherpesvirus subfamily of herpesviruses
• Genome: Double stranded DNA- 170kbp’s
• Target Cell: T-lymph
• limited nucleotide homology.
• It is thought HHV6/7 is similar to HHSV.
• Causes: Roseola

HHV 6 and 7: Epidemiology/ Pathogenesis

• Common: Worldwide
• Saliva, Breast feeding- HHV 6/7
• Maternal antibody over 4% of the maternal count is removed
• Adulthood will contain 90- 99% of both viruses over time due to immune function
• remains in the body.

Description and Symptoms of Roseola

• Is a common viral infection that effects Infants of early child hood
• Mostly infecting children between the ages of 6 and 24 months otherwise known as sixth disease, exanthem, rosale

Roseola symptoms

• Patients may have an upper illness,
• Followed with heat
• In certain heat they will not eat and show swollen glands in the neck
• Has a pinkish-red flat that appears, in high heat over the trunk after a fever

Roseola Cont.

• Fast rising fever that comes with roseola
• Febrile seizure occurs.
• This may be a sign- Loss of control of the limbs, face and bowl

Roseola Diagnosis and Treatment

• Isolation is complicated and cannot be performed as a routine method
• serology where specific IgM and IgG are detected as a basis of the diagnosis for treatment
• Highly contagious, transferred through breathing, contact with saliva or sneeze
• Can infect kids without being seen
• Treated with Acetaminophen or ibuprofen
• There is no specific way to antiviral

HHV 8 (KSHV)

• Belongs to the subfamily
• Recently discovered Kaposi
• Commonly has tumors

Pathogenesis of HHV-8 (KSHV)

• Kaposi's sarcoma herpesvirus (KSHV)
• Is of low Seroneagtive due
• Groups with susceptibility contains saliva.
• It contains the factor of high titers in DNA

HHV-8: Associated diseases

• Kaposi's Sarcoma
• lymphoma
• Castleman's disease
• pulmonary hypertension

Characteristics of HHV-8 Transmission and Treatment

• Sexually transmitted
• From parent to children
• Organ Transplants Cryotherapy
• Chermothearpy
• Laser treatment

Papillomavirus- Diseases

• 80% of Papilloma occur in female species
• Cause squamous cells -
• HPV is associated

HPV Properties

• Affects our mucosal and skin linings of the genital area from sexual transfer
• HPV 1/4 Causes planter warts
• 2,3,10 causes warts

Describing Warts

• Finger like
• Has a flat
• grow as external force pushes inwards
• dysplsia
• verrucriformis

HPV Transmission

• Transmission can occur from skin to skin contact and during genital contact
• Genital and skin warts
• Affects people with lowered immune function, in both children and adults
• Viruses can with stand being on animate areas for a period of time

HPV Pathogenesis

• squamous epithelial is induced in cells with the HPV virus
• Abnomial growth of cells
• Karocytes or in benign growths

Signs of HPV

• Hard sores and warts can grow
• If flat, it can spread outward, forming caner
• Varies of the virus are often spread during sex.

Treatment of Warts and Cervical Lesions

• Accomplised through the removel of abnormal cells
• Karyotic - ice or nitrogen
• Burning with metal or removal
• Treatment in cervical requires surgery

Immunosuppressed and HPV

• They have more extensive HPV
• Women are contracted at a high rate

Explore the characteristics, transmission, and diagnostic methods for Herpes Simplex Virus (HSV) and Varicella-Zoster Virus (VZV). Understand the challenges in curing HSV, VZV latency, and diagnostic approaches for identifying and managing related infections. Learn about the accurate differentiation between HSV-1 and HSV-2.