Med Micro mizzou 3200 final

viruses cannot___ or ___ independent of host cel

generate energy or produce proteins

viruses do not have the genetic capability to multiply by

division

Viruses genome??

RNA OR DNA, NOT both

single stranded or double stranded

viruses have a naked ____ with attached____

capsid or envelope, proteins

virion

the infectious particle consisting of the envelope(some viruses), capsid and the interior core (genome +/-accessory viral proteins)

capsid

the outer protein shell that protects the interior core containing the genome and other proteins

genome

genetic material of the virus, either DNA or RNA

reduces transmission

-high rates of replication are often very damaging to host tissues which can kill the host

-high rates of replication are more likely to stimulate an immune response

increases transmission

genome/virion stability within host cells

tissue tropism

range of tissue types that a virus can infect

hit and run viral strategy

(small pox)

-viral production very high

-exposure relatively short

-large number of virions increases the likelihood of transmission (short-term)

Slow and low

(HEP. C)

-viral production very low

-exposure relatively long

-Immune evasion strategy

latency with occasional reemergence

(herpes simplex virus)

-viral production is moderate

-exposure is life long-viral genome integration

-transmission is relatively targeted

Icosahedral capsids

radial symmetry, based on polyhedron with 20 identical triangular faces

ex- herpes simplex virus (HSV)

filamentous capsids

helical symmetry, helical tube around the genome, which is wound helically within the tube

length can extend to 50x its width, generating flexible filament

ex- tobacco mosaic virus, Ebola virus

bullet shaped capsid

rabies virus

amorphous capsid

pox viruses

pleomorphic capsid

ebola virus

Avian Leukosis Virus (ALV)

small RNA retrovirus containing 3 genes--gag, pol, env

form 9 functional products

pandoravirus salinus

largest known virus to date

antigenic drift

virions no longer recognized by neutralizing antibodies

generates new strains of virus that can cause serious disease-classic ex is influenza virus

viral evolution

1. host community- evolve to preferentially infect different host species

2. viral species population- strains evolve that vary infectivity and virulence (ex- HHV1 and HSV2 cause similar diseases and HHV3 and HHV5 cause distinct diseases)

3. individual host organism- viruses evolve variants that resist therapeutic agents(HEP C & HIV)

Baltimore Model viral classification

-genome composition (DNA or RNA)

-whether it is single- or double-stranded

-If it is single stranded, whether the strand encodes proteins or requires synthesis or a complement that encodes proteins

7 baltimore groups

Group 1 of Baltimore model

Human Herpes Virus Double-stranded DNA is transcribed to mRNA

Group 2 of Baltimore model

Parovirus

single-stranded DNA

generates a double-stranded form within the host cell, which is transcribed to mRNA

Group 3 of Baltimore model

Rotavirus

double-stranded RNA

makes mRNA by using RNA-dependent RNA polymerase

Group 4 Baltimore model

Polio virus

single-stranded RNA(+)

makes complementary(-) strand which is transcribed to mRNA

Group 5 of Baltimore model

Influenza

Single-stranded RNA(-) is transcribed to mRNA

Group 6 of Baltimore model

HIV

single-stranded RNA(+) is reverse-transcribed to DNA, which is transcribed to mRNA

group 7 of Baltimore

HEP B

Double-stranded DNA is transcribed to mRNA which is reverse-transcribed to make viral genomes for packaging into virions

lytic replication

replication cycle usually results in death and lysis of host cell

stages:

attachment & entry

synthesis and assembly

exit and transmission

direct penetration

viral capsid of genome is translocated directly into cytoplasm

membrane fusion

viral envelope fuses w the PM releasing the nucleocapsid into the cytoplasm--> capsid breaks down

endocytosis

virion-receptor complex is endocytosed into cytoplasm

viral envelope fuses w the endosomal membrane releasing nucleocapsid---> capsid breaks down to release genome

DNA viruses typically enter where and why

nucleus- they require the host cell's DNA-dependent RNA polymerase

where do RNA viruses typically replicate?

cytoplasm

HP DNA Genome

-HPV gains access to the actively dividing cells of the epidermis basal layer

-virions are endocytosed by the basal cells (but no replication until basal cells start to differentiate into keratinocytes)

-as epithelial layers slough off, progeny virions are shed

-sometimes HPV virions become latent, persisting for months or years & the latent viral genomes may induce host cells to form abnormal growths, such as warts or cancers

viral pathogenesis in general derives from

-latency

-cell death/damage

-Immune-mediated damage

properties of true latency

maintenance

persistence

reversibility

episomal latency

use of episomes during latency (extra-chromosomal genetic material that may replicate autonomously) --herpes

proviral latency

occurs when the viral genome is integrated into the host chromosome(s)--retroviruses such as HIV-1

cell death (viral pathogenesis cytopathic effects)

can be virally-Induced lysis(adenovirus) or cellular apoptosis (poliovirus)

cell fusion (viral pathogenesis cytopathic effects)

certain viruses promote cell-cell fusion to generate, giant multinucleate cells (HIV,RSV)

malignant transformation (viral pathogenesis cytopathic effects)

certain viral infections can lead to cellular transformation ---cancer development

cytotoxic t cells - (viral pathogenesis immune mediated injury)

HAV & HBV both stimulate production of CTLs which kill infected hepatocytes--accounts for majority of damage to the liver

immune complex deposition (viral pathogenesis immune mediated injury)

HBV-antibody complexes can become deposited on capillary membranes--> immune mediated vasculitis

plaque assay

1. infect monolayer w virus

2. remove liquid medium

3. add gelatin medium

4. virus reproduces, host cells lyse...forming plaques

this can be used to estimate the number of infectious particles (plaque-forming units, pfu) in a sample

PCR

Direct detection of viral genomic material, high sensitivity can detect both DNA & RNA viruses, can multiplex. screen for multiple pathogens in a single sample

acute coryza (rhinitis) commonly assoc. w -

rhinoviruses, coronaviruses

influenza commonly assoc. w-

influenza viruses

Croup is commonly assoc. w -

parainfluenza viruses

Bronchiolitis commonly assoc. w-

RSV

Bronchopneumonia

influenza virus, RSV, Adenoviruses

influenza pathogenesis

1.direct cell lysis (primary) upper/lower respiratory tracts--edema/inflammation

2. role of immune response -primarily protective rather than pathogenic, induces virus- and type-specific immunity, virus-mediated suppression (NS1 protein)

major complications influenza virus infections

secondary bacterial pneumonia- (superinfection) -> death aka S. pneumonia, H. influenzae, S. aureus

classic signs and symptoms of severe influenza infection

rapid onset of symptoms

fever- over 38.5

early, nonproductive cough and headache

severe myalgia and fatigue

runny/stuffy nose

sore throat

seizures, night/cold sweats, no appetite, vomiting & diarrhea(cell breakdown products in body)

influenza A antigenic drift

due to gene shuffling and reassortment

requirements:

segmented genome (8RNA segs)

multiple HA & NA subtypes in environment

animal reservoir (wild aquatic birds)

susceptible species for both avian and human influenza to undergo recombination (swine)

infleunza treatment

neuraminidase inhibitors

-oseltamivir(tamiflu, oral)

-zanamivir (relenza, inhaled)

-peramivir (rapivab, IV)

common cold symptoms not related to flu

high fever is rare

headache is rare

myalgia is mild flu is severe

fatigue is mild and flu is sever and prolonged

Rhinoviruses

baltimore group 4

non-enveloped

non-segmented (+) single stranded RNA genome

at least 100 serotypes are known

sensitive to low pH (no GI infection)

optimal growth at 32 degrees- adaption to nasal cavity

rhino viral pathogenesis

minimal direct virus-Induced cell damage

primarily upper respiratory tract

immune response (histamine release) correlates w symptoms

responsible for COPD & asthma exacerbations

induces serotype-specific immunity

coronaviruses

baltimore group 4

pleomorphic, enveloped virus

non-segmented(+) ss-RNA genome

6 human serotypes known- 4 commonly infect humans causing common cold

compared to rhinoviruses-- longer incubation period and shorter symptoms

SARS-CoV & MERS-CoV= rare and life-threatening

Adenoviruses

baltimore group 1

non-enveloped

icosahedral nucleocapsid containing linear dsDNA

at least 57 serotypes

causes 3-5% of respiratory infections in children, less than 2% in adults

Clinical manifestations of adenoviruses

rarely cause serious illness of death

mostly just

common cold-mostly in young kids

pink eye

bladder inflammation or infection (cystitis)

acute respiratory disease (ARD)

sever acute respiratory syndrome (SARS)

emerged in china 775 deaths

SARS caused by the SARS-associated coronavirus (SARS-CoV)

insidious flu-like symptoms --> atypical pneumonia based on CXR

fever greater than 38 degrees C

20-30% respiratory failure, ventilator

lower GI- diarrhea

paramyxoviridae

visions are enveloped-spherical, filamentous or pleomorphic

genome is non-segmented, -ssRNA, 6-10 genes

Group 5

respiratory syncytial virus

parainfluenza viruses

mumps

measles

human metapneumovirus

Hendra, Nipah

Parainfluenza virus

infect respiratory epithelium, large airways

3 major envelope proteins

Haemagglutinin (H)-binds to cell surface

Neuraminidase (N)- release from cell surface

Fusion(F) protein-promotes membrane fusion

clinical manifestations of parainfluenza

5 mil hospitalizations in US each year under 5 years old

often promotes secondary bacterial infection (otitis media)

acute laryngo-tracheo bronchitis (croup), severe URI of infants (6-48 mos)

croup

mild URI initially

barking couch

hoarseness

sore throat

stridor (airway obstruction)

clinical diagnosis based on symptoms

chest xray reveals characteristic "steeple sign"

RSV- respiratory syncytial virus

classified into groups A&B by sera

cytolytic infections of bronchiole epithelium

primary infection of young kids

adults are at increased risk of bronchial asthma

RSV formation

envelope contains Fusion(F) protein- viral entry and syncytium formation

syncytial-giant, multinucleate cells

Bronchiolitis

URI

then cough, wheezing and difficulty breathing (dyspnea), chest x ray reveals hyperinflation

severe:

poor feeding, lethargy history of apnea, respiratory rate under 70/min, severe chest wall recession, cyanosis (blue coloring or skin and mucuous membranes due to poor o2)

pt.s may require 02, intubation or mechanical ventilation

viruses assoc. w gastroenteritis(stomach flu)

-rotavirus

-norovirus

-adenovirus types 40, 41, &52

-astrovirus

NOT: picornaviridae

Rotavirus

infants and children (~100& by age 5)

adults in US--> child care workers, elderly, travelers

Strain A- 90% of infection in humans

infects/damages mature enterocytes leading to severe malabsorption and loss of disaccharides(2ndary lactose intolerant) - osmotic type diarrhea

Gastroenteritis-mild to severe disease symptoms

watery, dark green, explosive diarrhea

vomiting, abdominal pain

low-grade fever

lasts 3-5 days can cause dehydration

Rotavirus Non Structural Protein 4 (NSP4)

first identified viral enterotoxin

stimulates enteric nerves--hyperperistalsis (overactivity of intestinal muscles)

stimulates Vagus nerve-- promotes vomiting

stimulates salt and water secretion -- secretory type diarrhea

dx- ELISA, PCR

rx- ORS

Norovirus

leading cause of food borne illness in US

transmitted

fecal-oral

person to person contact

aerosolization of vomited virus

classic scenarios for outbreak- cruise ships

pathology of norovirus

shortening of enterocyte villi

crypt cell damage

decreased digestive enzymes (lipase & disaccharidases)

damage to laminitis propria due to immune cell infiltration

diseases assoc. w poliovirus (enteroviruses)

paralytic poliomyelitis

diseases assoc. with coxsackle group A (enteroviruses)

hand, food and mouth disease

skin & mucosa membranes

diseases assoc. with coxsackle group B (enteroviruses)

myopericarditis, pericarditis

heart, pleura, pancreas, and liver

diseases assoc. with echovirus (enteroviruses)

aseptic meningitis, rash, febrile illness, conjunctivitis, severe generalized neonatal disease

diseases assoc. with Enterovirus (enteroviruses)

polio-like illness, hemmorrhagic conjunctivitis (E70)

Polio virus

human specific pathogen

highly contagious (oral-oral, fecal-oral)

following ingestion--> virus multiples within GI mucosa--> transient viremia 75% of patients, asymptomatic

25% symptoms in 2-5 days

fever, sore throat, tiredness, nausea, headache, stomach pain

paralytic poliomyelitis

~1% infections, poliovirus invades and replicates within motor neurons

motor neuron death leads to flaccid paralysis-muscle atrophy over time

many cases result in only temp. paralysis

Hepatitis A (infectious hepatitis) transmission

fecal-oral - food handlers (raw fruits/veggies), raw shellfish, water supply

close personal contact- household contact, sexual contact, child day care centers

blood exposure (rare) - injecting drugs, transfusions

Clinical features of hep A

incubation period 3-4 wks

general symptoms- flu-like, fever/chills, body aches, fatigue, nausea/vomiting

jaundice by age group <14-0-50%

>14-70-80%

complications- relapsing, cholestatic hep., fulminant hep.

HAV diagnosis

HAV-IgM- 1-14 wks post infection

HAV-IgG- clearance of infection (high titers indicate protection)

ALT- liver enzyme (releases due to liver damage)

HEP B (serum hepatitis)

"Dane particle" = infectious form

Hep. B transmission

Sexual- predominant transmission route

Perinatal- mothers HBeAg positive--predominant in endemic populations like s.e Asia

Parenteral-needle stick in none immune, 30%.. rare-surgeon, dentist, medical equipment

HBV Pathogenesis

primary infection: viremia->liver->replicates in hepatocytes (not cytotoxic)

replication involves RNA intermediate (HBV reverse transcriptase)

HBV clinical features

-incubation period- 90 days

-general symptoms- poor health, loss of appetite, nausea, vomiting, aches, mild fever, dark urine

-chronic hepatitis

HBV Treatment

most adults clear infection spontaneously

-reverse transcriptase inhibitors (lamivudine, adefovir dipivoxil, entecavir, telbivudine, tenofovir) - all drugs active against HIV to some extent

HEP C

Most common chronic blood borne infection

causes 40% of chronic liver disease

incubation period 7-8 wks

75% are subclinical

symptoms mild and vague - acute liver failure

85% of adults have a chronic infection

CD4+ T cells normal range

450-1500

oral candidiasis is common in

HIV+ (10-40%) of pts.

AIDS (90%) of pts.

tests for HIV

HIV ELISA test

Western blot

Retroviruses

-contain two, noncovalently linked copies of the (+) ssRNA genome --> pseudodipliod

-nucleocapsid is surrounded by an envelope that contains spikes formed by a virus-encoded glycoprotein

-virion contains 10-50 copies of reverse transcriptase

-Integrase enzymes -- provirus integration

two types: primarily oncogenic and primarily immunosuppressive

HIV-1

is encountered globally and accounts for the majority of infections in North America and Europe

HIV-2

characterized by a longer asymptomatic stage and lower mortality , progression to AIDS does occur

largely restricted to Western Africa