micro viruses and buzz words

parvovirus

ssDNA, icosahedral, naked.

- smallest DNA virus.

epidemiology: respiratory transmission. can cross placenta

pathogenesis: targets erythroid precursors

symptoms: fever and rash. rash is initially on cheeks then spreads to extremities

papova- papilloma

stimulates cell growth and DNA synthesis

Human Papillomavirus:

dsDNA, naked, icosahedral

Epidemiology:

direct contact

- serotype 2 and 4: common, plantar and flat warts

sexual transmission

- genital warts

- low risk HPV 6 and 11

- high risk HPV 16, 18, 31, 35

Pathogenesis:

- virus enters through breaks in skin (warts)

- flesh colored papules

Diagnosis- koilocytes on pap

adenovirus

dsDNA, naked, icosahedral

Epidemiology:

Fecal- Oral, fingers, fomites, swimming pools

Pathogenesis: infections epithelial cells in oropharynx, respiratory, and enteric tracts

Symptoms:

Swimming pool conjunctivitis (pharyngitis with pink eye)

Epidemic keratoconjunctivitis (pink-eye)

Acute respiratory tract disease

- fever, cough, pharyngitis, cervical adenitis

Poxvirus

Most complex virus. linear, dsDNA genome, enveloped, replication in cytoplasm

- encodes own DNA dependent RNA polymerase

Examples:

- orthopox (smallpox)

- molluscipox (molluscum contagiosum)

- monkeypox

poxvirus

Smallpox (Variola)

Epidemiology:

- respiratory droplets and close contact

- first disease successfully eradicated

Pathogenesis:

- Virus infects all dermal tissues and internal organs

- synchronous rash

Cowpox

- vaccina

- used as live, attenuated vaccine

Herpesvirus

liner, dsDNA, icosahedral

- envelope derived from nuclear envelope

Once infected, virus remains

Herpesvirus differs from other DNA viruses:

- encodes own DNA- dependent DNA polymerase (not carried in virion)

- acquires envelope from nuclear envelope

Diagnosis:

- Clinical Symptoms

- VZV can be isolated from skin lesions

- PCR, immunofluorescence

- Tzank smear

- Multi- nuclear giant cells (syncytia) with intranuclear inclusions

Examples of Herpesvirus

HSV- 1 (cold sores and STD)

HSV-2 (STD)

Varicella- Zoster virus (VZV)- chickenpox and shingles

Epstein- Barr virus (EBV)- mononucleosis

Human Cytomegalovirus (CMV)- mainly asymptomatic disease, birth defects in fetus

Human herpesvirus- 6 (HHV-6 and 8)- roseola and AIDS related disease

Latency and Reactivation of Herpesvirus

latency: no protein expression or viral DNA replication, but viral DNA is detected

HSV 1- Trigeminal Ganglia

HSV 2- Sacral Ganglia

VZV- Dorsal Root Ganglia

EBV, CMV and HHV-6 - white blood cells

reactivation: latency terminated and virus begins replication

Varicella Zoster Virus (VZV)

Herpesvirus.

Chickenpox:

Transmission:

- respiratory (highly contagious)

- direct contact with skin lesions

Disease:

- Asynchronous rash (crops of lesions)

- progresses from maculopapular to vesicular to crusting scabs

Zoster- Shingles (reactivation)

- Due to reactivation of latent VZV from ganglia

- Disease: painful, itchy dermatomal rash, does not cross midline

Hepadnavirus

Hepatitis B virus (HBV)

- Small, enveloped, icosahedral DNA virus

- Has reverse transcriptase- RNA intermediate

- surrounded by HB core antigen (HBcAg)

- Envelope contains HB surface antigen (HBsAg) glycoprotein

- HB e antigen (HBeAg) is minor component of active virion

Epidemiology:

- Spread via sexual, blood or perinatal transmission

- blood, sharing needles, acupuncture, ear piercing, tattooing

Pathogenesis:

- virus replicates in hepatocytes

- CD8 T cells kill virally infected cells causing jaundice

- HBV genome integrates into hepatocytes (months later)

Clinical disease:

- acute: jaundice, dark urine and pale stools

- chronic (5-10% of infections): cirrhosis and liver failure. primary hepatocellular carcinoma (80% attributed to HBV)

Diagnosis:

PCR for viral DNA, serology used to categorize pts

caliciviruses

Norwalk virus (Norovirus)

(+) ssRNA, naked, icosahedral

Transmission: direct contact, fecal/oral, fomites

- risk factors: close living quarters (dorms, military and cruise ships)

Pathogenesis: compromise function of intestinal brush border

Symptoms:

- Diarrhea and nausea (no blood in stools)

- Fever in 1/3 of pts

- Incubation time of 24-48 hours

Diagnosis: Electron microscopy, radioimmunoassay, ELISA

Picornaviridae

small (+)ssRNA, naked, icosahedral

Enteroviruses: polio, coxsackie a and b, hepatitis A, echoviruses and enteroviruses

Rhinoviruses

Poliovirus

Picornaviridae.

Epidemiology: fecal- oral transmission

Pathogenesis:

- polio must get to brain to cause myelitis

- very narrow tissue tropism

- dorsal root ganglia, motor neurons, skeletal muscle cells and lymphoid cells

Clinical disease:

Paralytic polio- severe muscle pain and spasms, followed by weakness. lower limbs affected more than upper limbs. Progress to flaccid paralysis with no sensory loss

Flaviviridae

(+)ssRNA, enveloped, icosahedral

- Arthropod borne viruses (arboviruses): yellow fever, zika virus, dengue, west nile encephalitis, st. louis encephalitis, Japanese encephalitis.

- Hepatitis C virus

Epidemiology:

- Mosquito is most common vector

- Birds and small mammals are reservoirs

Pathogenesis:

Female mosquitoes transmit virus

- 1 degree viremia produces flu like symptoms in 3-7 days

- most infections do not progress beyond this point

- 2 degree viremia affects organs

- brain, liver, skin, vasculature depending on tissue tropism of virus

Yellow Fever: Central and South America, Caribbean, Africa.

Clinical disease (~15% of cases)- Jaundice (yellow fever) with black vomit

Zika Virus:

- Adults- intense myalgia

- Congenital infections- microcephaly

Matonaviruses

(+)ssRNA, enveloped, icosahedral

- Exanthemous (skin rash/eruptions)

Rubella virus (german measles, 3-day measles):

- Transmission: respiratory secretions

- Symptoms:

-Fever, malaise, lymphadenopathy then irregular maculopapular rash

- rash begins on face/forehead, spreads to trunk and extremities

- Congenital rubella syndrome

Coronavirus

(+)ssRNA, enveloped, helical

Transmission: Respiratory Droplet

SARS- Severe Acute Respiratory Syndrome:

- Interstitial pneumonia with high fever

- 2002- 2004 - disappeared after brief outbreaks

SARS- CoV- 2

- Covid- 19 pandemic

- Interstitial pneumonia with high fever

- Receptor is angiotensin converting enzyme 2

Retrovirus

(+) ssRNA, enveloped, icosahedral

Retrovirus RNA genome is converted into DNA, which is integrated into the host chromatin and transcribed as the host gene

Human Immunodeficiency Virus (HIV)

- uniquely brings two single stranded positive RNA copies.

- RNA- dependent DNA polymerase (reverse transcriptase)

- Integrase- pathogen's genome is integrated into our genome

- Protease- cuts up protein so the little pieces have their own function

Has 3 major genes: gag (structural proteins), pol (enzymes) and env (envelope proteins and glycoproteins)

HIV viral entry and time course of disease

gp120 (VAP) binds to CD4 and CCR5/CXCR4

- infects T cells (& some macrophages)

- gp41 aids viral and cell membrane fusion

- individuals with CCR5 mutation are resistant to infection

Time Course:

- initial symptoms may resemble the flu

- AIDS- related complex (ARC)

- fever, weight loss, lymphadenopathy

- AIDS- Acquired Immunodeficiency syndrome

- lack of CD4 T cells

- Death due to opportunistic infection

Paramyxoviridae

(-)ssRNA, enveloped, helical

Can all induce cell to cell fusion (to form syncytia)

Measles (Rubeloa)

Paramyxoviridae

Transmission: respiratory secretions before and after symptoms

Pathogenesis: cell fusion, giant cells

Clinical Symptoms:

Fever, 3 C's and photophobia

- cough, coryza, conjunctivitis

Koplik spots

- small red spots with bluish white speck in center

Maculopapular rash

- starts below ears and spreads on body

Complications:

giant cell pneumonia, encephalitis, subacute sclerosing panencephalitis

Mumps

Paramyxoviridae

Transmission: respiratory secretions

Clinical symptoms:

- flu- like symptoms with bilateral swelling of parotids (salivary glands)

- CNS involvement

- Pancreatitis, deafness, orchitis

Prevention: MMR vaccine

- about 50% of children infected before vaccine

Rhabdoviruses

(-)ssRNA, enveloped, helical

Rabies:

Transmission:

Racoons in US, wild dogs world wide

Pathogenesis:

- Infects peripheral nerves

- Binds to nicotinic acetylcholine receptor

- Retrograde axonal transport to dorsal root ganglia, spinal cord

Clinical:

Acute neurological period. Furious episodes interspersed with calm episodes

- agitation, hyperactivity, restlessness, thrashing, biting, confusion, hallucinations

- hydrophobia- causes people to be afraid of water because water will dilute the virus

- coma -> death (almost always fatal without intervention)

Diagnosis:

- History of animal bite

- PCR

- Negri bodies

- cytoplasmic inclusions where virus assembly occurs

Filovirus

(-)ssRNA, filamentous (helical but extra long), enveloped, helical

High mortality rate- moves very quickly

Ex: ebolavirus, marburgvirus

Orthomyxovirus

(-)ssRNA, enveloped, helical

Influenza:

8 segments.

Influenza A- animals and humans

Viral Structure: Hemagglutinin (HA): attachment to cell

- binds sialic acid on cell surface

- Neuraminidase (NA): cleaves new virus from sialic acids, liquefies mucous, helps viral release

Antigenic Drift:

minor changes in genome due to error prone viral RNA polymerase. All influenza types. Endemics

Antigenic Shift:

Major changes in genome usually due to exchange of gene segments. Pandemic- ex Spanish flu was bird to human, and swine flu was bird-pig- human

Transmission: small airborne droplets

Pathogenesis: ciliated cell death in URT. impairment of mucociliary clearance can cause secondary infection

Clinical disease (1-4 day incubation)

- flu like symptoms, headache and weakness, fever, chills, myalgia, non- productive cough

Bunyavirus

(-) ssRNA, segmented, enveloped, helical

Zoonotic viruses -> animals to human

Ex; Hantaan, California Encephalitis, Lacrosse, Rift Valley Fever

Arenaviruses

(-)ssRNA, helical, enveloped

Ex:

Lymphocytic choriomeningitis virus (LCMV)- aseptic meningitis, encephalitis

Hemorrhagic fever viruses: lassa, junin, machupo

Viruses cause persistent infections in rodents- can be transmitted by zoonoses

Reoviruses

segmented dsRNA, naked, icosahedral, brings polymerase

Rotavirus:

Transmission: fecal- oral

Common in infants and toddlers (daycares)

Clinical: gastroenteritis, no blood or inflammatory cells

incomplete dsDNA genome

Hepadnavirus (Hepatitis B)

replicates DNA via RNA intermediate

Hepadnavirus (dsDNA)

ssDNA virus

Parvo

replicates RNA via DNA intermediate

Retrovirus (+) RNA

dsRNA

Reovirus

Syncytia

Herpesvirus, retrovirus, paramyxoviruses

Owl's eye inclusions

CMV, adenovirus

Cowdry Type A

HSV and VZV, measles virus

Guameri bodies

small pox

negri bodies

rabies

nuclear envelope

herpesvirus

slapped cheek fever

parvovirus

koilocytes

Human Papilloma (HPV)

swimming pool conjunctivitis

adenovirus with pharyngitis

Epidemic keratoconjunctivitis (pink- eye)

adenovirus. no pharyngitis

complex capsid

poxvirus

dermatomal rash

Zoster- Shingles (Herpesvirus)

Black vomit

Yellow fever (Flaviviridae)

koplik spots

Measles (Rubeola)- Paramyxovirus

bullet shaped virus

rhabdoviruses- rabies

filamentous virus

filoviruses