Herpes, Varicella, and Small Pox Flashcards
1
Q
Herpesviridae
A
- Large group of viruses widespread throughout the animal kingdom
- Human herpesviruses are ubiquitous
- Many individuals become infected at an early age
- Latent infection and recurrent disease are trademarks of herpesvirus infection
- Linked to human cancer
- EBV ⇒ Burkitt’s lymphoma and nasopharyngeal carcinoma
2
Q
Herpes Simplex Virus (HSV)
Overview
A
- First human herpesviruses recognized
-
Two types of HSV ⇒ types 1 and 2
- Share many common Ag
- Have specific glycoproteins that distinguish them
- Differ in many biological characteristics
3
Q
HSV
Structure
A
- Icosahedral capsid
- Capsid enclosed in a glycoprotein-containing envelope
- Acquired as it buds through host cell nuclear membrane
-
Tegument ⇒ space between envelope and capsid
- Contains viral proteins
- Sensitive to acid, solvents, detergents, and drying
4
Q
Herpesvirus
Genome
A
Genomes of the five well-defined HHV have a unique organization:
- Long, double-stranded linear DNA molecules
- Several repeated and inverted sequences
5
Q
HSV
Glycoproteins
A
HSV virions contain at least 11 glycoproteins:
- gB, gD, and gH ⇒ attachment and entry into the cell
-
gD ⇒ essential for infection
- Varies little in structure and antigenicity between HSV-1 and HSV-2
-
gC differs extensively between HSV-1 and HSV-2
- Antisera to gC generally type specific
6
Q
HSV
Infection
A
- Can infect most types of human cells & other animals
- Virus receptor expression on many types of cells ⇒ broad host range
- HSV-1 and HSV-2 can infect the same tissues and cause similar diseases
- Predilection for specific infection sites and disease patterns
- Infection generally results in:
- Lytic or productive infections of fibroblast and epithelial cells
- Latent infections of neurons
7
Q
HSV
Cell Entry
A
-
HSV-1 initially binds to heparan sulfate
- Proteoglycan found on the outside of many cell types
- Then interacts w/ a protein closer to the cell surface
- Major route of HSV penetration is fusion at the cell surface membrane
- Virions can also enter cells by endocytosis
- Nucleocapsid enters cytoplasm
- Capsid docks w/ nuclear membrane
- Delivers the genome into the nucleus ⇒ where transcription and replication occur
- Virion proteins carried in the tegument also delivered into the cell
8
Q
HSV
Protein Synthesis
A
Transcription and protein synthesis occurs in 3 regulated phases:
-
Immediate-early (IE)
- DNA-binding proteins
- Stimulate DNA synthesis and promoter transcription of early viral genes
-
Early (E)
- Mostly of enzymes required for replicating the viral genome
- DNA-dependent DNA polymerase
- Scavenging proteins
- Deoxyribonuclease
- Thymidine kinase
- Ribonucleotide reductase
- Provide substrates for replication, even in cells not undergoing DNA synthesis (neurons)
- Mostly of enzymes required for replicating the viral genome
-
Late (L)
- Many copies of these proteins are required for virion assembly
- Each phase is required for progression to the next
9
Q
HSV
Dissemination
A
- Capsid proteins are transported to the nucleus
- Assembled into empty procapsids
- Filled w/ DNA
- DNA-containing capsids associate and bud from viral glycoprotein-modified portions of the nuclear membrane
- Virus also released when cell lysis occurs
10
Q
HSV
Primary Infection
A
- HSV usually causes a localized infection
- Enters body via mucosal membranes or breaks in the skin
- Viral replication @ site of entry ⇒ inapparent or produce vesicular lesions
- Replicates in cells @ base of lesion
- Vesicular fluid contains infectious virus
- Lesion generally heals w/o producing a scar
11
Q
HSV
Cellular Effects
A
- HSV can cause lytic infections of a variety of cell types
- HSV replication generally leads to cytolysis due to:
- Virus-induced inhibition of cellular macromolecular synthesis
- Degradation of host cell DNA
- Membrane permeation
- Cytoskeletal disruption
- Senescence of the cell
12
Q
HSV
Latency
A
- Virus spreads to adjacent cells and innervating neurons
- After infection of the neuron, nucleocapsid transported to cell nucleus ⇒ virus latency
- Latent infection of neurons results in no detectable cytopathic alteration of neurons
- Few, if any virus-specific proteins detectable during latent phase
13
Q
HSV
Reactivation
A
-
Virus can be activated from the neuron by various stimuli (e.g., stress, trauma, fever, or sunlight)
- Reactivation occurs despite presence of neutralizing Ab
- Trigger usually involves stress w/ ± transient depression of CMI
- Virus travels back down the nerve ⇒ lesions at the dermatome
- Recurrent infections usu. less severe, more localized, and of shorter duration
14
Q
HSV
Host Immune Response
A
- During primary infection, interferon and NK cells help limit progression of infection
- IFN ⇒ ⊕ NK cells ⇒ recognize HSV-infected targets and lyse cells
- MΦ phagocytize viral Ag ⇒ present to CD4 helper T cells and B cells ⇒ ⊕ antigen-specific immunity
-
Control and resolution requires both humoral and cellular immunity:
- Ab vs virus glycoproteins ⇒ neutralize extracellular virus ⇒ limits spread
- Ab vs HSV-1 protective against future challenges by other strains of HSV-1
- Also to some extent against infections w/ HSV-2 and vice versa
-
Virus can escape neutralization and clearance by:
- Direct cell-to-cell spread
- Latent infection of the neuron
-
CMI essential for controlling and resolving HSV infections
- Absence of CMI ⇒ dissemination to vital organs and brain
- Cellular immune and inflammatory responses ⇒ immunopathologic ∆ ⇒ sx exacerbation
15
Q
HSV
Transmission
A
-
Virus found in oropharyngeal secretions
- Spreads by direct contact
- Presumably requires salivary exchange
-
HSV-2 primarily transmitted by sexual intercourse
- May infect the genitalia, anorectal tissues, or oropharynx
- Associated w/ symptomatic or asymptomatic primary infection or recurrences
- Asymptomatic recurrences are especially likely in females
- May shed the virus in cervical secretions w/o any clinical illness
- Most new cases of genital HSV result from sexual contact w/ individuals who have active lesions
- Should refrain from sexual intercourse when prodromal sx or lesions occur
- Can resume only after lesions are completely re-epithelialized
- Virus can be isolated from lesions even when crusted
-
Vertical transmission may also result from:
- Maternal viremia during primary HSV-2 infection
- Ascending in utero infection
- Infection during delivery
20
Q
Varicella-zoster virus (VZV)
Pathogenesis
A
Predominant means of spreading VZV is by the respiratory route.
21
Q
Varicella
A
“Chickenpox”
Primary infection caused by VZV
- Usually a disease of childhood
- Usually symptomatic, although asymptomatic infection may occur
- Incubation period of about 14 days
- Characterized by fever and maculopapular rash
- Lesion progression: maculopapular → vesicle on M/P base (“dew drop on a rose petal”) → pustule → crust → scab
- Successive crops of lesions appear for 3 to 5 days
- At any given time, all stages of skin lesions can be observed
-
Rash is generalized
- More severe on trunk than extremities
-
Notably present on the scalp
- Distinguishes it from many other diseases
- Lesions are very pruritic ⇒ scratching ⇒ ± bacterial superinfection and scarring
- Varicella is a risk factor for acquiring invasive infection w/ Group A Strep (S. pyogenes)
- Mucous membrane lesions in the mouth, conjunctivae, and vagina typical
- ± Thrombocytopenia ⇒ ± hemorrhagic rash
- Primary infection of adults usu. more severe than for children
- ± Interstitial pneumonia (20-30% of adult pts) and may be fatal
- Extremely severe, disseminated infection occurs in immunocompromised pts
22
Q
Herpes Zoster
A
Recurrent infection with VZV
- Occurs sporadically in pts who had varicella infection in the past
- Appearance of chickenpox-like lesions usually preceded by severe pain in innervated area
-
Rash usually unilateral and occurs in one or more adjacent dermatomes
- Small, closely spaced maculopapular lesions on erythematous base
- Lesions vesiculate rapidly and often coalesce
- Following a zoster infection, pts may experience a chronic pain syndrome ⇒ postherpetic neuralgia
- Can persist for months to years
- Occurs in up to 30% of pts who develop zoster after 65
25
Q
Poxviruses
Major Features
A
- Largest, most complex viruses
- Complex, oval to brick-shaped morphology w/ internal structure
- Multiple viruses in both categories 1° infect non-human vertebrates
- Two viruses only infect man ⇒ variola virus (Smallpox) and molluscum contagiosum
- DNA viruses that replicate in the cytoplasm
-
Assembly in cytoplasmic inclusion bodies ⇒ B-type inclusions, previously known as Guarnieri’s bodies
- Where it acquires its outer membranes
27
Q
Poxviruses
Genome and Proteins
A
- Linear, double-stranded DNA genome w/ fused ends
- Codes for wide range of proteins
- Encodes and carry all proteins necessary for mRNA synthesis
- Encodes proteins for DNA synthesis, nucleotide scavenging, and immune escape mechanisms
- Carry more proteins in particle
- Produce multiple proteins that interfere w/ host defenses
28
Q
Smallpox
Pathogenesis
A
Human is only host
Causes a disseminated respiratory tract infection
- Incubation: 5-17 days
- Initial replication in upper respiratory tract
- Systemic dissemination by lymphatics and cell-associated viremia
- Primary viremia ⇒ replication in multiple organs
- Secondary viremia often occurs
- Fever 3 days before rash
-
Slow-onset centrifugal rash due to hemorrhage of small blood vessels
- Extensive pustules all at the same stage, usu. involves palm and soles
- Mortality:
- 15–40% (Variola major)
- 1% (Variola minor)
31
Q
Molluscum contagioisum
A
- Spread by contact w/ lesion
- Results in wart-like growth w/ caseous plug
- Warts usually occur in clusters
- Incubation: 2-8 weeks
- Characteristics: Eosinophilic cytoplasmic inclusion in cells
- Self-limiting: disappears in 2-12 months
- Treatment: iodine, liquid nitrogen
32
Q
Poxviruses
Disease Mechanisms
A
- Smallpox initiated by respiratory tract infection and spread mainly by lymphatic system and cell-associated viremia
- Molluscum contagiosum and zoonoses are transmitted by contact
- Virus may cause initial stimulation of cell growth and then cell lysis
- Virus encodes immune escape mechanisms
- Cell-mediated immunity and humoral immunity are important for resolution
34
Q
Varicella vs Small Pox
A
