SJSU MICR20 CHAPTER 25

RNA viruses

- diverse group of microbes

- assigned to 1 of 12 families absed on envelope, capsid, & nature of RNA genome

influenza

- 3 distinct influenza virus types: A, B, C (type A causes most infections)

- virus attaches to, & multiplies in cells of respiratory tract

- segments of RNA genome enter nucleus

- finished viruses are assembled & bud off cell

influenza glycoproteins

- key to influenza are glycoprotein spikes

- Hemagglutinin (H)

- Neuraminidase (N)

- both glycoproteins frequently undergo genetic changes, decreasing effectiveness of host immune response

Hemagglutinin (H)

- 15 subtypes

- most important virulence factor

- binds to host cells

Neuraminidase (N)

- 9 subtypes

- hydrolyzes mucus & assists viral budding & release

influenza mutation

- constant mutation; gradually change their amino acid composition (antigenic drift)

- antigenic shift

- genome of virus consists of 10 genes encoded on 8 separate RNA strands

antigenic shift

one of the genes or RNA strands is substituted w/ a gene or strand from another influenza virus from a different animal host

antigenic drift

- constant mutation

- gradually change their amino acid composition

influenza strains

- influenza nomenclature chronicles virus type, animal of origin, location, & year of origin

- influenza A, B , & C

influenza A

- acute, highly contagious respiratory illness

- seasonal, pandemics; among top 10 cause of death in US

- most common in elderly & small children

- most virulent

- underwent antigenic shift from only infect bird to humans

influenza B

- only undergo antigenic drift, no antigenic shift

influenza C

- known to cause only minor respiratory disease; probably not involved in epidemics

influenza A symptoms

- rapid shedding of cells, stripping respiratory epithelium; severe inflammation

- fever, headache, myalgia, pharyngeal pain, shortness of breath, coughing

- weakened host defenses predispose patients to secondary bacterial infections, especially pneumonia

enveloped nonsegmented ssRNA viruses

- rhabdoviruses (rabies)

- coronaviruses (COVID-19)

- flaviviruses (Hep. C)

- filoviruses (ebola virus)

Rabies

- virus enters through bite, grows at trauma site for a week

- multiplies, then enters nerve endings & advances toward ganglia, spinal cord, & brain

- infection cycle completed when virus replicates in salivary glands

- skunk, raccoon, fox

clinical phases of rabies

- prodromal phase

- furious phase

- dumb phase

- progress to coma phase, resulting in death

prodromal phase (rabies)

- fever, nausea, vomiting, headache

- some pain, burning, tingling sensations at site of wound

furious phase (rabies)

agitation, disorientation, seizures, twitching, hydrophobia

dumb phase (rabies)

paralyzed, disoriented, stuporous

Coronaviruses

- relatively large RNA virus w/ distinctively spaced spike on their envelopes

- common in domesticated animals

- 5 types of human coronaviruses characterized

agents of coronavirus

- common cold

- some forms of viral pneumonia & myocarditis

- some human enteric infections

- severe acute respiratory syndrome (SARS)

Severe Acute Respiratory Syndrome (SARS)

- newly emerging disease (2020)

- transmitted through droplet or direct contact

- fever, body aches, & malaise

- may or may not experience respiratory symptoms w/ breathing problems

- severe cases result in respiratory distress & death

- diagnosis relies on exclusion of other likely agents

- treatment is supportive

Hepatitis C

- caused by flavivirus (HCV)

- acquired through blood contact (blood transfusions, needle sharing)

- infections w/ varying characteristics

- treatment w/ interferon & ribavirin to lessen liver damage; no cure

- no vaccine

Hepatitis C: characteristics

- 75 to 85% will remain infected indefinitely

- possible severe symptoms w/o permanent liver damage

- more common to have chronic liver disease, w/o overt symptoms

- cancer may result from chronic HCV infection

Hemorrhagic fevers

- yellow fever

- dengue fever

yellow fever

- eliminated in U.S.

- two patterns of transmission: urban cycle & sylvan cycle

- acute fever, headache, muscle pain

- may progress to oral hemorrhage, nosebleed, vomiting, jaundice, & liver & kidney damage

- significant mortality rate

urban cycle

- human & mosquitoes

- Aedes aegypti

Sylvan cycle

- forest monkeys & mosquitoes

- South American

Dengue fever

- flavivirus carried by Aedes mosquito

- not in U.S.

- usually mild infection

- Dengue hemorrhagic shock syndrome

Dengue hemorrhagic shock syndrome (breakbone fever)

- extreme muscle & joint pain

- can be fatal

Human immunodeficiency virus (HIV)

- acquired immunodeficiency syndrome

- retrovirus, in genus Lentivirus

- first emerged in early 1980s

- first documented case of AIDS: 1959

HIV symptoms

- severe pneumonia caused by Pneumonocystis jirovecci

- rare vascular cancer called Kaposi sarcoma

- sudden weight loss, swollen lymph nodes

- general loss of immune function

characteristics of human retroviruses

- encode reverse transcriptase (RT) enzyme

- viral genes permanently integrated into host DNA

- cause of acquired immunodeficiency syndrome (AIDS)

reverse transcriptase

enzyme which makes a double stranded DNA from the single stranded RNA genome

HIV infection causative agent

- HIV-1 & HIV-2

- T-cell lymphotropic viruses 1 & 2 (leukemia & lymphoma)

- HIV can only infect host cells that have required CD4 marker + co-receptor

epidemiology of HIV infection

- 1st nationally notifiable in 1984

- 6th most common cause of death among people 25-44 in U.S.

- men account for 75% of new infections

- IV drug abusers can be HIV carriers; significant factor in spread to heterosexual population

- 2009, # of infected individuals worldwide: 35M; 1.2M in U.S.

pathogenesis & virulence factor of HIV

- HIV enters through mucous membrane or skin

- travels to dendritic phagocytes beneath epithelium

- multiplies & shed

- virus taken up & amplified by macrophages in skin, lymph organs, bone marrow, & blood

- HIV attaches to CD4 & co-receptor; HIV fuses w/ cell membrane

- reverse transcriptase enzyme makes DNA copy of RNA

- viral DNA is integrated into host chromosome

- can produce lytic infection or remain latent

stage of HIV infection & AIDS

- pathology tied to 2 factors: level of viruses & level of T cells in blood

- primary effects & secondary effects of HIV

primary effects of HIV infection

- extreme leukopenia - lymphocytes in particular

- formation of giant T cells & other syncytia - virus spreads

- infected macrophages release virus in CNS, with toxic effect (inflammation)

secondary effects of HIV

- CD4 lymphocytes destruction

- opportunistic infections &U malignancies during full-blown AIDS

Hepatitis A virus & infection

- multiplies in small intestine & enters blood & then carried to liver

- most infections subclinical or vague, flu-like symptoms occur; jaundice is seldom present

Hepatitis A virus transmission

- cubical picornavirus relatively resistant to heat & acid

- not carried chronically

- principle reservoirs are asymptomatic, short-term carriers or people with clinical disease

- fecal-oral transmission

Hepatitis A virus treatment

- no specific treatment once symptoms begin

- inactivated & attenuated viral vaccines

- pooled immune serum globulin for those entering into endemic areas

Hantavirus

- transmitted: contact w/infected rodent urine, droppings, or saliva

- symptoms: Hantavirus pulmonary syndrome (HPS)

- prevention: avoid rodent exposure, proper sanitation

Hantavirus pulmonary syndrome (HPS)

Mumps

- paramyxovirus

- transmission: respiratory droplets

- symptoms: swelling of salivary glands, fever, headache, muscle aches

- prevention: MMR vaccine (measles, mumps, rubella)

Ebola

- filovirus

- transmission: direct contact w/bodily fluids of infected individuals

- symptoms: fever, severe headache, vomiting, diarrhea, hemorrhagic signs

- prevention: avoid contact w/infected persons, vaccination in outbreak areas

Measles

- paramyxovirus

- transmission: airborne respiratory droplets

- symptoms: high fever, cough, runny nose, characteristic rash

- prevention: MMR vaccine

prion

- misfolded forms of proteins, lack nucleic acids

- induce normal proteins in brain to misfold, causing chain reaction

- results in neurodegeneration

spongiform encephalitis

- group of progressive neurodegenerative disease

- caused by prions

- characterized by sponge-like changes in brain tissue

- Creutzfeldt-Jakob disease

Creutzfeldt-Jakob disease (CJD)

- most common human prion disease

- rapid cognitive decline & neurological symptoms

Koplik Spots

- small, bluish-white lesions that appear on inner linings of the cheeks

- pathognomonic sign of measles

- appear 1-2 days before measles rash

Exanthem

- widespread rash associated w/measles

- appear after initial symptoms

- rash begins 3-5 days after onset of fever & other symptoms

- starts as small, red spots that can merge to form larger patches

- typically begin at hairline, spread downward across body

MMR vaccine

- Measles, Mumps, Rubella vaccine

- combination vaccine that protects against three viral diseases

- typically give in 2 doses: 12-15 months, 4-6 year

MERS-COV

- Middle East Respiratory Syndrome-Coronavirus

- first identified 2012 in Saudi Arabia

- transmission: camels to humans, limited human-human transmission

- severe respiratory illness, fever, cough, & gastrointestinal symptoms

- 34% fatality rate

SARS-CoV-2

- Sever Acute Respiratory Syndrome-Coronavirus 2

- identified Dec. 2019 in Wuhan, China

- transmission: respiratory droplets, aerosols, contact w/contaminated surfaces

- fever, cough, fatigue, difficulty breathing, loss of taste/smell, pneumonia

West Nile Virus (WNV)

- mosquito-borne virus (Culex species)

- cause neurological disease in human

- many asymptomatic

- fever, headache, body aches, encephalitis or meningitis

Zika virus

- mosquito-borne virus (Aedes species)

- mild illness; fever, rash, joint pain, conjunctivitis

- linked to serious birth defects when pregnant women infected

gp41

- forms a fusion complex that helps virus penetrate host cell

- crucial role in fusion process, bringing viral & cellular membranes together

gp120

- acts as a key for virus to attach to & enter host cells

- variable regions contribute to virus's ability to evade immune system

protease inhibitors

- class of antiviral drugs that inhibit protease enzyme

- enzyme essential for maturation of HIV

- by blocking enzyme, prevent virus from maturing into infectious form; prevent cleavage of viral polyproteins into functional proteins necessary for viral replication

integrase inhibitors

- class of antiviral drug that block integrase enzyme

- enzyme responsible for inserting HIV DNA into host cell's genome

- stops virus from replicating

Cellular Prion Protein (normal PrPc)

- alpha-helical structure

- found in healthy cells, especially in brain

- role in cell signaling, neuroprotection & regulation of neurodevelopment

- generally stable & doesn't induce disease

Scrapie Prion Protein (abnormal PrPsc)

- misfolded & insoluble

- forms aggregates that are resistant to proteases

- converts normal proteins into abnormal, misfolded proteins

- associated w/prion diseases, leading to neurodegeneration & brain damage