Viral Skin and Soft Tissue Infections Flashcards
What are the three subfamilies of Herpesviruses? How many are considered human herpesviruses?
- Alphaherpesviruses
- Betaherpesviruses
- Gammaherpesviruses
8 are considered human herpes viruses
What three viruses fall in the alpha herpesvirus family?
Herpes Simplex Virus 1 (HSV-1)
Herpes Simplex Virus 2 (HSV-2)
Varicella-Zoster Virus (VZV)
What is the B virus?
A monkey alpha herpesvirus which can infect humans only by bite, and can result in fatal encephalitis
What three viruses fall in the beta herpesvirus family?
Cytomegalovirus (CMV)
Human Herpesvirus 6A and 6B (HHV-6A, HHV-6B)
Human Herpesvirus 7 (HHV-7)
What two viruses fall in the gamma herpesvirus family?
Epstein-Barr Virus (EBV)
Human Herpesvirus 8 (HHV-8)
What causes herpes labialis, and what age group does it affect most?
HSV-1 more often than HSV-2, “cold sores”
Affects children and adolescents most
What causes genital herpes?
HSV-2 > HSV-1
What is another common HSV-1 complication?
Keratoconjunctivitis, which can cause blindness
What are some of the rarer HSV-1 complications?
dermatitis, encephalitis, disseminated HSV (in immunocompromised)
Who is most likely to be infected with a systemic HSV-2 infection which is very dangerous?
Neonates, general herpes and encephalitis can be very severe
What is the definition of HSV latency?
Continued presence of viral genome in lysogenic cycle, in the absence of viral replication / particles. Latency always happens and lasts a lifetime
How does HSV latency initially occur?
HSV enters into nerve cells, is transported to the relevant sensory ganglion, and viral replication occurs in the ganglion for several days before latency occurs
When does HSV reactivation occur? What initiates it and where does it occur?
Spontaneously, often induced by sunburn, stress, menstruation, or immunocompromisation
Activated by a neuron-specific JNK kinase pathway
Virus replicates and travels back down the axon to cause infection by the site of primary infection
What is the structure of HSV and its genome?
Large, enveloped DNA virus with icosahedral capsid
Linear, ds DNA genome with about 80 genes
What is the process of HSV attachment to integration into genome?
Virion attaches via heparan sulfate on cell surface, and is either endocytosed or directly fuses with virion envelope.
Capsid is transported to nuclear pore via microtubules, and released into the nucleus
What are the three phases of HSV gene expression?
- Immediate early genes adapt cell for virus replication
- Early genes produce / replicate viral DNA
- Late genes include structural proteins
Where is the viral DNA packaged into capsids and then ultimately released?
In the nucleus, packaged into capsids.
Naked capsid passes into cytoplasm via temporary envelop of nuclear membrane, then is finally enveloped via Golgi apparatus
What are two key HSV-coded enzymes?
- DNA Polymerase
2. Thymidine Kinase (TK)
What is the mechanism of acyclovir?
Nucleotide analog to thymidine.
Phosphorylated by HSV’s TK to acyclovir monophosphate, then made into triphosphate by cellular kinases.
This acyclovir-trisphosphate functions to:
- inhibit viral DNA polymerase
- terminate nascent viral DNA strands
What is valacyclovir? Does this work on latent virus?
The prodrug form of acyclovir with higher bioavailability
Neither this or acyclovir will work on latent virus
What are complications of varicella?
Pneumonia, inflammation of brain or spinal cord, congenital birth defects
Where does latent VZV stay?
Dorsal root ganglia
What is Varicella, and how is it transmitted? (include first infection to a second infection)
Chickenpox
Virus which initially enters upper respiratory tract, spreads to lymphoid organs and replicates there
Second stage spreads to epithelial tissue causing lesions and respiratory tract for further transmissino
What is the incubation period of varicella, and how do the lesions progression?
12-14 days, lesions progress centrifugally (trunk first, then outward to face and limbs).
Macule -> papule -> vesicle -> crusting which heals without scarring
What is Zoster and how does it typically begin?
Shingles, recurrence of latent VZV
Typically begins with nerve pain / post-herpetic neuralgia
Where does Zoster occur? How can it be prevented?
Lesions are generally limited to skin / mucous membrane innervated by reactivated ganglion
It can happen multiple times, and is preventable via Zostervax, a stronger version of childhood chickenpox vaccine
What are the general characteristics of beta herpesvirus infections?
Restricted host range and cell type specificity
What is HHV-6A vs HHV-6B vs HHV-7? What is the relative prevalence?
HHV-6: wide cell tropism, preferential T cell replication.
HHV-6A - no clear disease association
HHV-6B - associated with exanthem subitum (roseola), stays latent in monocytes / macrophages
HHV-7 - T cell tropic, latent in T cells
Most people are seropositive for both
What is the clinical presentation of Exanthem subitum (roseola)?
Common childhood infection
Fever lasts 3-5 days, followed by a rash as fever diminishes, accompanied by upper respiratory symptoms
What are complications of roseola?
High fever, aseptic meningitis, hepatitis, mononucleosis-like syndrome
Where is HHV-8 of high prevalence? What class of herpesviruses is it?
Gamma herpesviruses
HIgh prevalence in sub-Saharan Africa and Mediterranean region, low prevalence elsewhere except HIV-1 positive
What is HHV-8 associated with?
Kaposi’s sarcoma, and lymphomas / lymphoid hyperplasia
What is Classic Kaposi’s Sarcoma (KS)?
Slow progression, typically found in Mediterranean men, nodular / plaque-like dermal lesion in lower leg
What is Endemic-African KS?
More aggressive KS, with lymph node involvement
What is Iatrogenic KS?
Induced via solid-organ transplant patients (immunocompromised), common in Mediterranean
What is the lymphadenopathic form of KS and who is it typically foundin?
Disseminated and aggressive, involving internal organs, viscera, lymph nodes, and skin
Seen in HIV patients
What is the structure of papillomaviruses?
Non-enveloped icosahedral
Circular dsDNA with 8-10 genes
What are papillomaviruses known for?
Cutaneous and mucosal warts, condylomas (genital wards), and papillomas
What are the two major transforming genes of the HPV-16 genome?
E6: Causes destruction of p53 tumor suppressor protein
E7: Inactivates Rb tumor suppressor protein (controls G1->S)
What is the major vaccine target of HPV?
L1 gene product, a major capsid protein, active component of Gardasil HPV vaccine
What types of cutaneous warts does HPV cause? What is one HPV type common to cause this?
Common wart - painless and hyperkeratotic
Plantar wart - painful, deeply set on weight-bearing surfaces of foot
Flat warts - multiple flat, assymmetric papules
HPV 2 commonly causes this
What types of mucosal warts does HPV cause? What HPV types are associated with these and cancer?
Laryngeal, oral, and conjuctival papillomas -> HPV 6 and 11
Anogenital papillomas -> 6 and 11 also cause these, but weak cancer association
Types 16 and 18 are uncommon but papillomas often progress to cervical cancer
What is the range of clinical outcomes to HPV infection?
Subclinical infection with full clearance to high grade lesions with carcinoma
What are condylomata?
plural of condyloma, or genital warts (includes anus)
Where does HPV infection occur in the skin? What does it initially do? How is it spread?
The basal cell layer (quite superficial)
Initially induces hyperplastic growth to keep the skin growing fast for viral spread
Mature virus is only released in highly keratinotic cells (stratum corneum), and is spread by direct contact or fomites
What stage of HPV Cervical Intraepithelial Neoplasia (CIN) is difficult to differentiate from condylomata? What does this correspond to?
CIN1, about 1/3 of the stratum layer is abnormal thick and hyperplasic
What are the next stages of CIN?
CIN2 = 2/3 of skin
CIN3 = 3/3 of skin = carcinoma in situ
Invasive cancer -> infects lower tissue
Metastatic cancer -> invades other body tissues
What is Gardasil protective against? Cervarix? How young can they be?
Gardasil - HPV types 6,11,16, and 18
Cervarix - HPV 16 and 18 (just cancer)
Can be as young as 9 years old
What is the structure of Picornaviruses and what is one example?
Small, non-enveloped viruses with ssRNA (+) genomes
example: Coxsackieviruses (especially A)
How are picornaviruses spread?
Saliva, mucous, or feces
What are two diseases caused by picornaviruses?
- Hand, Foot, and Mouth Disease - blisters / ulcers on all these areas, typical in Asia
- Herpangina - includes only the mouth lesions
What are general clinical symptoms of Coxsackie virus infections?
Common in infants in children, general malaise like fever, sore throat, headache, vomiting, convulsions
Specifically: Small papulovesicular lesions on tonsils and soft palate, as well as hands and feet in HFMD. Lesions heal within 1-5 days.
Rapid resolution vs HSV infection
What is vaccinia virus used for?
Live virus used to immunize against smallpox (Variola). Temporary skin lesion is left.
What is molluscum contagiosum?
A type of Poxvirus, leaves Wart-like bumps which resolve in 6-12 weeks, spread by contact
What is orf?
A zoonotic poxvirus which can be spread via sheep / goats.
