Clinical Microbiology Refresher

Microbes That Cause Infectious Diseases

prokarya→bacteria

eukarya:

• fungi (yeast+molds)

• protozoa

• helminths (worms)
  -multicellular

viruses:

• no membrane+cytoplasm

• can’t make own energy

• unable to synthesize proteins

Important Features of Cellular Microbes

structure:

cells: nucleus/nucleoid containing DNA

• surrounded by cytoplasm

• proteins synthesized

• energy generated

viruses: inner core of genetic material (DNA/RNA)

• no cytoplasm

• depend on host cells for energy

method of replication:

cells:

• binary fission

• mitosis

viruses:

• must replicate within host cells

• disassemble→produce copies of nucleic acids+proteins→reassemble into viruses

nature of nucleic acid:

cells: both DNA and RNA

viruses: either DNA or RNA but not both

Eukaryotes vs Prokaryotes

eukaryotes:

• DNA in nucleus within nuclear membrane

• multiple chromosomes

• histones

• organelles

• larger ribosome 80s

• flexible plasma membranes (fungi→chitin cell walls)

• cell membrane contains sterols

• divide by mitosis (fungi→budding)

prokaryotes:

• DNA in nucleoid region

• no nuclear membrane

• single circular chromosome

• no histones

• no organelles

• smaller ribosome 70s

• rigid peptidogycan cell walls

• no sterols in cell membrane (exc: mycoplasma)

• divide by binary fission

General Terminology/Nomenclature

bacteria/fungi/protozoa/helminths: genus+species
ex: escherichia (genus) coli (species)

virus: name-virus
ex: poliovirus

Peptidoglycan

• a complex interwoven macromolecule network

• surrounds entire cell

• composed of a single covalently linked macromolecule

polymer of a prepeating disaccharide in rows:

n-acetylglucosamine (NAG)
n-acetylmuramic acid (NAM)
NAM-NAG complex
linked by polypeptides

• found only in bacterial cell walls

• rigid support for cell

• maintains shape of cell

• gives cell resistance to low osmotic pressure

Microscopy Staining

gram stain:

• bacteria

• fungi

acid-fast stain:

• mycobacteria

calcofluor white stain:

• fungi

gomori methenamine silver (GMS) stain:

• fungi

Cell Wall

gram-positive: thicker cell wall

gram-negative: thinner cell wall

acid-fast: glycolic walls

atypical: PCR-based testing needed

Gram Positive+Aerobic: Staphylococci

all catalase positive

coagulase-positive→staph aureus

coagulase-negative:

• staph lugdunensis

• staph epidermis

• staph saprophyticus

• staph haemolyticus

Gram Positive+Aerobic: Streptococci

all catalase-negative

beta-hemolysis:

• strep pyogenes (group A strep)

• strep agalactiae (group B strep)

alpha-hemolysis:

• strep pneumoniae

• viridians group strep

non-hemolysis:

• enterococcus faecalis

• enterococcus faecium (harder to treat)

Gram Positive+Aerobic: Bacilli

listeria monocytogenes

bacillus anthracis

corynebacterium diptheria

Gram Negative+Aerobic: Cocci

neisseria meningitidis

neisseria gonorrhoeae

haemophillus influenzae

moraxella catarrhalis

Gram Negative+Aerobic: Spirochetes

trepodema pallidium (syphillis)

borrelia burgdorferi (lyme disease)

Gram Negative+Aerobic: Bacilli

lactose-fermenting:

oxidase-negative:

• enterobactales

• escherichia coli

• klebsiella

• enterobacter cloacae

• citrobacter

• serratia spp

• providencia spp

• proteus spp

oxidase-positive:

• aeormonas spp

• pasteurella spp

• vibrio spp

non-lactose-fermenting:

oxidase-negative:

• acinetobacter baumanii

• sternotrophomonas spp

• burkholderia spp

oxidase-positive:

• pseudomonas aeurginosa (nosocomial)

Anaerobes: Cocci

gram positive: peptostreptococcus spp

gram-negative: veillonella spp

Anaerobes: Bacilli

gram-positive:

• clostridioides/clostridium difficile (c-diff)

• clostridium perfringens

• clostridium tetani

• clostridium botulinum

gram-negative:

• bacteroides spp

• prevotella spp

• fusobacterium spp

Atypical Bacteria

chlamydia pneumonia

chlamydia trachomatis

mycoplasma pneumoniae

legionella pneumophila

Acid-Fast Bacteria

myocbacterium tuberculosis

mycobacterium avium complex

nocardia spp

actinomyces

Classification of Medically Important Bacteria

based on nature of cell wall:

rigid:
-free-living
-non-free-living

flexible→spirochetes

absent→mycoplasmas

used under genera+species

Gram-Positive Medically Important Bacteria

Gram-Negative Medically Important Bacteria

Atypical Medically Important Bacteria

Staphylococcus Aureus

PP: gram-positive cocci
grape-like clusters

R: human→nose

E: abscesses

various pyogenic infections:
-endocarditis
-septic arthritis
-osteomyelitis)

food poisoning
scalded skin syndrome
toxic shock syndrome

CM: post-surgical wound infections

pneumonia:

• empyema

• lung abscess

conjunctivitis:

• unilateral burning eye pain

• hyperemia of conjunctiva

• purulent discharge

abscesses

scalded skin syndrome

impetigo

carbuncle

osteomyelitis

septic arthritis

P: pneumonia
septicemia
surgical-wound infections

skin+soft tissue infections (SSTIs):
-folliculitis
-cellulitis
-impetigo

bacterial conjunctivitis

Streptococcus Pyogenes

PP: gram-positive cocci
chains or pairs

CM:
pyogenic dx:

• pharyngitis

• cellulitis

toxigenic:

• scarlet fever

• toxic shock syndrome

immunologic dx:

• rheumatic fever

• acute glomerulonephritis

group A:

• cellulitis

• erysipelas

• necrotizing facsiitis

• impetigo

P: group A→pharyngitis

cellulitis

group-B→neonatal sepsis

E. Faecalis: UTI
endocarditis

S. Viridians→endocarditis (rare)

Clostridium Spp.

PP: gram-positive rods
anaerobic
spore-forming

E/P:
clostridium perfringens: gas gangrene
food poisoning

clostridium difficile

Mycobacteria

mycobacterium tuberculosis→tuberculosis

mycobacterium leprae→leprosy

mycobacteria avium-intracellulare complex (MAI, MAC)→tuberculosis-like dx

mycobacterium kansasii→tuberculosis-like dx

mycobacterium chelonae→immunocompromised/implant amputee dx

Spirochetes

treponema: syphillis
non-veneral treponematoses
yaws
pinta
E: direct contact

borrelia: lyme disease
relapsing fever
E: infected tick

leptospira: leptospirosis

E: animals
animal urine contaminated water

CM: 7-13 day asx incubation period→CM
fever
chills
headache
conjunctival suffusion
myalgia

Viruses (General)

not considered cells

not capable of independent replication→must reproduce within cells (obligate intracellular parasites)

can’t make own energy+proteins

too small to be seen with microscope

particles composed of internal core with DNA/RNA (not both) covered by protein coat
±outer lipoprotein membrane→envelope

don’t have: nucleus
cytoplasm
mitochondria
ribosomes

Pathogenesis of Viruses+Stages of Viral Infection

pathogenesis:

1. transmission of virus→entry into host

2. replication of virus→damage to cells

3. spread of virus to other cells+organs

4. innate+adaptive immune responses activate

5. potential persistence of virus

stages of infection:

1. incubation period→asx

2. prodromal period→nonspecific sx

3. specific-illness period→CM sx

4. recovery period→dx wanes→pt normal health

Herpesvirus

PP: replicate in nucleus→form intranuclear inclusions
obtain envelope from nuclear membrane

E:
HSV-1: saliva
face infections

HSV-2: sexual contact
genital infections

CM:

HSV-1: above the waist

• acute gingivostomatitis

• recurrent herpes labialis (cold sores)

• keratoconjunctivitis (keratitis)

• encephalitis

• erythema multiforme

HSV-2: below the waist

• herpes genitalis (genital herpes)

• neonatal encephalitis

• neonatal herpes

• aseptic meningitis

• erythema multiforme

Respiratory Viruses

PP: infect respiratory tract→infect mucosal cells of respiratory tract→cause sx in respiratory tract+CM found outside respiratory area
most have RNA (one has DNA)
most enveloped (exc: rhinovirus+adenovirus)

E: measles
mumps
rubella
varicella zoster
orthomyxoviruses
paramyxoviruses
coronaviruses

CM: found outside respiratory tract

DX: severe→PCR-based assay from respiratory tract secretions

Human Immunodeficiency Virus (HIV)

PP: infects+kills CD4/helper T lymphocytes→suppression+loss of cell-mediated immunity (destroys immune system)→opportunistic infections

E: retrovirus
HIV-1→worldwide
HIV-2→west africa
caused by acquired immunodeficiency syndrome (AIDS)
humans+certain primates
non-endogenous to humans (no sequences found in normal human cell DNA)

CM:

1. early/acute

2. middle/latent

3. late/immunodeficiency

P: opportunistic infections

Fungi Structure

eukaryotic organisms

different from prokaryotic bacteria

2 medically important fungal structures:

fungal cell wall: made of chitin (not peptidoglycan)
insensitive to certain cell-wall synthesis-inhibiting abx (penicillins/cephalosporins)

contain other polysaccharides: beta-glucan (long polymer of D-glucose+site of action for caspofungin)

chitin: polysaccharide
composed of long chains of N-aceytlglucosamine

fungal cell membrane: contains ergosterol (not cholesterol)

Fungi Growth

yeasts:

• unicellular

• budding→daughter cells unequal in size

molds:

• multicellular

• contain hyphae/long filaments of cells

• cell division→daughter cells equal in size

sexual reproduction spores:

• classified by sexual spores

• zygospores→single large+thick walls

• ascospores→formed in ascus sac

• basidiospores→formed externally on tip of pedestal called basidium

dimorphism:

• exist as yeasts or molds depending on temperature

• mold→room temperature

• yeast→body temperature

Parasite Classification

protozoa:

• single-celled

• classified on most important site of infection:
  -giardia→intestines
  -trichomonas→urogenital
  -plasmodium→blood
  -tissue→toxoplasma

metazoa:

• multicellular

• helminths/worms

two phyla:

platyhelminthes: flatworms
cestoda→tapeworms
trematoda→flukes

nemathelminthses: roundworms
nematodes

Protozoa Forms+Transmission

trophozoite:

• motile/feeding/reproducing form of protozoan

• flexible cell membrane

cyst:

• non metabolizing/nonreproducing form of a protozoan

• thick wall

transmission:

intestinal protozoa→ingestion of cysts

blood+tissue protozoa→insect vectors
exc: toxoplasma→ingestion of cysts from cat feces/placenta transfer

Helminths Transmission

life cycle: egg→larva→adult

transmission:

1. ingestion of eggs

2. penetration of skin by larvae

3. insect bite

DX: stool→ova+parasites

Microbiology DX Process

1. pt infected

2. 1-3 hrs→specimens collected+sent to lab

3. automated culture system/agar plate

4. 
   

no growth: incubate for over 5 days

growth: rapid dx test in 1-3 hr
gram stain T-24h in 1 hr→24-48 hr→identified microorganism

Minimum Inhibitory Concentration (MIC)

lowest concentration of an abx that inhibits visible growth

Dx: broth microdilution (BMD)
disk diffusion/kirby-bauer
epsilometer strip/e-test

automated: vitek2
microscan walkaway plus system

Interpretation of Phenotypic Susceptibility Results

breakpoints/interpretive criteria: Breakpoints at which successful eradication of an organism has been confirmed in practice, as established by the Clinical and Laboratory Standards Institute (CLSI M100)

criteria:
susceptible (S)
susceptible dose dependent (S-DD)
intermediate (I)
resistant (R)

Contaminant

organism present in a culture specimen that is deemed to not be the primary cause of infection

occurs by chance+improper technique/cross-contamination

interpreting contaminants as pathogens could expose pt to unnecessary abx

Colonizer

an organism present at a body site but doesn’t normally cause sx

often not pathogenic

may be symbiotic

Ex: healthy GI flora is essential for healthy GI tract

Gut Microbiota

the microorganism and viruses that live within the colon

Gut Microbiome

the genome of the gut microbiota which is used for identification through sequencing

Prebiotics

fiber that can pass through the upper GI undigested

Probiotics

live microorganisms that can be ingested for health benefits

Pathogen

any organism/microorganism that can cause disease in its host

Opportunistic Pathogen

a microorganism

in healthy individuals→typically does not cause disease

in weakened/compromised immune system→causes disease

Virulence

the capacity of a microorganism to cause disease

Infectious Dose

the minimum number of pathogenic organisms/pathogens required to establish an infection/disease in a host

Gram Positive vs Gram Negative Bacteria+Gram Stain

gram positive

• thick peptidoglycan layer

• retain purple stain

gram negative

• thin peptidoglycan layer+outer membrane

• turn pink after stain

gram stain

• determines difference between gram positive/gram negative bacteria

• stain order: gram positive→gram negative

Role of Cell Wall With Physical Signs and Medications

Bacteria

• possess a cell wall→made of peptidoglycan

• exception→Mycoplasma

• Gram-negative bacteria

• have a thin peptidoglycan layer

• covered by an outer lipid membrane→contain endotoxin→a key inducer of septic shock

Gram-positive bacteria

• have a thick peptidoglycan layer

• no outer membrane

periplasmic space

• in gram-negative bacteria

• between inner+outer membranes

• houses β-lactamases→enzymes→degrade β-lactam antibiotics

Peptidoglycan (unique to bacteria)

• forms a network providing shape

• composed of:
  -sugar backbone
  -peptide side chains
  -(both) cross-linked by transpeptidase

Mycobacteria

• higher lipid content in cell wall→resistant to Gram staining

• susceptible to acid-fast staining

Lysozymes

• breaks down peptidoglycan's glycan backbone→destroys bacteria

cytoplasmic membrane

• regulates nutrient transport

• regulates toxin secretion

Fungi Types

yeasts

• single cells

• reproduce asexually→budding

molds

• long filaments→hyphae→form a mat→mycelium

• form transverse walls→septate hyphae

• don’t form transverse walls→nonseptate hyphae
  -multinucleated→coenocytic

Fungi Route of Transmission+Habitat of Medically-Important Fungi

TABLE 47–2Transmission and Geographic Location of Some Important Fungi

Genus	Habitat	Form of Organism Transmitted	Portal of Entry	Endemic Geographic Location
Coccidioides	Soil	Arthrospores	Inhalation into lungs	Southwestern United States and Latin America
Histoplasma	Soil (associated with bird feces)	Microconidia	Inhalation into lungs	Mississippi and Ohio River valleys in the United States; many other countries
Blastomyces	Soil	Microconidia	Inhalation into lungs	States east of Mississippi River in the United States; Africa
Paracoccidioides	Soil	Uncertain	Inhalation into lungs	Latin America
Cryptococcus	Soil (associated with pigeon feces)	Yeast	Inhalation into lungs	Worldwide
Aspergillus	Soil and vegetation	Conidia	Inhalation into lungs	Worldwide
Candida	Human body	Yeast	Normal flora of skin, mouth, gastrointestinal tract, and vagina	Worldwide

Laboratory Diagnosis of Fungi

Direct Microscopic Examination

• Specimens: sputum, lung biopsies, skin scrapings.

• Looks for hyphae, yeasts, and asexual spores.

• 10% KOH dissolves tissue while leaving fungi intact.

• Important findings:

  • Coccidioides immitis → spherules

  • Cryptococcus neoformans → wide capsule seen with India ink

• Calcofluor white binds fungal cell walls and fluoresces, making fungi easier to see.

• Methenamine silver stain can also highlight fungi in tissue.

Culture

• Usually performed on Sabouraud agar.

• Its low pH and antibiotics inhibit bacterial growth and favor fungi.

• Fungi can be identified by:

  • Mycelium appearance

  • Asexual spore characteristics

PCR

• Uses DNA probes to identify fungal organisms.

• Can identify fungi faster than waiting for colonies to become visually recognizable.

• Available for organisms such as:

  • Coccidioides

  • Histoplasma

  • Blastomyces

  • Cryptococcus

Serology

• Detects antibodies in serum or spinal fluid

• Particularly useful for systemic mycoses

• Diagnosis→significant rise in antibody titer

Complement fixation can be used for:

• Coccidioidomycosis

• Histoplasmosis

• Blastomycosis

• Cryptococcal meningitis: detects C. neoformans capsular polysaccharide antigen in CSF using latex agglutination.
  -known as the CRAG (cryptococcal antigen) test

Medical Mycoses

don’t need to know opportunistic mycoses

Bacteria vs Fungi (Table)

TABLE 47–1Comparison of Fungi and Bacteria

Feature	Fungi	Bacteria
Diameter	Approximately 4 μm (Candida)	Approximately 1 μm (Staphylococcus)
Nucleus	Eukaryotic	Prokaryotic
Cytoplasm	Mitochondria and endoplasmic reticulum present	Mitochondria and endoplasmic reticulum are absent
Cell membrane	Sterols present	Sterols absent (except Mycoplasma)
Cell wall content	Chitin	Peptidoglycan
Spores	Sexual and asexual spores for reproduction	Endospores for survival, not for reproduction
Thermal dimorphism	Yes (some)	No
Metabolism	Require organic carbon; no obligate anaerobes	Many do not require organic carbon; many obligate anaerobes

Opportunistic Fungi+5 Genera of Medically Important Fungi

immunocompetent→don’t cause disease

immunocompromised/impaired host defenses→cause disease

table→only need to know genus

TABLE 50–1Important Features of Opportunistic Fungal Diseases

Genus	Form in Tissue Seen by Microscopy	Geographic Location	Important Clinical Findings	Laboratory Diagnosis
Candida	Yeast forms pseudohyphae (also hyphae)	Worldwide	Thrush in mouth and vagina; endocarditis in intravenous drug users	Gram-positive; culture grows yeast colonies; Candida albicans forms germ tubes; polymerase chain reaction (PCR) assay; MALDI-TOF assay
Cryptococcus	Yeast with large capsule	Worldwide	Meningitis	India ink stain shows yeast with large capsule; culture grows very mucoid colonies; PCR assay
Aspergillus	Mold with septate hyphae	Worldwide	Fungus ball in lung; wound and burn infections; indwelling catheter infections; sinusitis	Culture grows mold with green spores; conidia in radiating chains
Mucor and Rhizopus	Mold with nonseptate hyphae	Worldwide	Necrotic lesion formed when mold invades blood vessels; predisposing factors are diabetic ketoacidosis, renal acidosis, and cancer	Culture grows mold with black spores; conidia enclosed in a sac called a sporangium

Dimorphic Fungi Properties+Pathogenesis+Important Clinical Findings

Clinical Features of Respiratory Viruses (Table)

Virus	Important Disease	Number of Serotypes	Causes Worldwide Epidemics (Pandemics)	Main Clinical Findings	Vaccine Available	Treatment
Influenza virus	Influenza	Many	Yes	Sudden-onset headache, shaking chill, sore throat, cough, and myalgias	Yes	Oseltamivir, zanamivir, baloxavir
Parainfluenza virus	Croup	Four	No	Barking cough	No	None
Respiratory syncytial virus	Bronchiolitis in infants	Two	No	Cough, dyspnea, retractions, wheezing	No	Ribavirin
Human metapneumovirus	Common cold, bronchiolitis, pneumonia	Two	No	Various (coryza, wheezing, cough)	No	None
Coronaviruses, especially SARS-CoV-2	Common cold, SARS,1 MERS,2 COVID-193	Seven (4 common cold serotypes; 3 pneumonia serotypes)	Yes	Various (coryza, cough, severe pneumonia)	Yes, for SARS-CoV-2	Remdesivir; Emergency Use Authorization for several drugs and monoclonal antibodies (see Text)
Rhinovirus	Common cold	Many	No	Runny nose (coryza), sneezing, no fever	No	None
Adenovirus	Pharyngitis, pneumonia, conjunctivitis	Many	No	Sore throat, cough, pneumonia, “pink eye”	Yes (for military only)	None

Clinical Features of Important Childhood Viruses (Table)

Virus	Important Disease	Number of Serotypes	Causes Worldwide Epidemics (Pandemics)	Main Clinical Findings	Vaccine Available	Treatment
Influenza virus	Influenza	Many	Yes	Sudden-onset headache, shaking chill, sore throat, cough, and myalgias	Yes	Oseltamivir, zanamivir, baloxavir
Parainfluenza virus	Croup	Four	No	Barking cough	No	None
Respiratory syncytial virus	Bronchiolitis in infants	Two	No	Cough, dyspnea, retractions, wheezing	No	Ribavirin
Human metapneumovirus	Common cold, bronchiolitis, pneumonia	Two	No	Various (coryza, wheezing, cough)	No	None
Coronaviruses, especially SARS-CoV-2	Common cold, SARS,1 MERS,2 COVID-193	Seven (4 common cold serotypes; 3 pneumonia serotypes)	Yes	Various (coryza, cough, severe pneumonia)	Yes, for SARS-CoV-2	Remdesivir; Emergency Use Authorization for several drugs and monoclonal antibodies (see Text)
Rhinovirus	Common cold	Many	No	Runny nose (coryza), sneezing, no fever	No	None
Adenovirus	Pharyngitis, pneumonia, conjunctivitis	Many	No	Sore throat, cough, pneumonia, “pink eye”	Yes (for military only)	None

Properties of Viruses Commonly Infecting the Intestinal Tract (Table)

Property	Norovirus	Rotavirus	Poliovirus	Coxsackie Virus	Echovirus
Virus family	Caliciviruses	Reoviruses	Picornavirus	Picornavirus	Picornavirus
Genome	Single-stranded RNA; positive polarity	Double-stranded RNA; 11 segments	Single-stranded RNA; positive polarity	Single-stranded RNA; positive polarity	Single-stranded RNA; positive polarity
Virion RNA polymerase	No	Yes	No	No	No
Nucleocapsid	Icosahedral	Icosahedral	Icosahedral	Icosahedral	Icosahedral
Envelope	No	No	No	No	No
Number of serotypes	Two or more	At least six	Three	Many	Many

Clinical Features of Viruses Commonly Infecting the Intestinal Tract (Table)

Property	Norovirus	Rotavirus	Poliovirus	Coxsackie Virus	Echovirus
Virus family	Caliciviruses	Reoviruses	Picornavirus	Picornavirus	Picornavirus
Genome	Single-stranded RNA; positive polarity	Double-stranded RNA; 11 segments	Single-stranded RNA; positive polarity	Single-stranded RNA; positive polarity	Single-stranded RNA; positive polarity
Virion RNA polymerase	No	Yes	No	No	No
Nucleocapsid	Icosahedral	Icosahedral	Icosahedral	Icosahedral	Icosahedral
Envelope	No	No	No	No	No
Number of serotypes	Two or more	At least six	Three	Many	Many

DNA Virus Classification

RNA Virus Classification

4 Main Effects of Virus Infection on the Cell

1. 4 main outcomes

   1. cell death
      viruses→stop protein production of cell→trigger apoptosis→cell death

   2. cell fusion
      infected cells→fuse together→form multinucleated giant cells
      ex:
      -herpesvirus
      -paramyxoviruses

   3. malignant transformation
      viruses→cause uncontrolled cell growth→contribute to cancer

   4. no obvious changes
      virus→replicates without causing noticeable changes/damage to cell

Viral Infections on Different Types of Cells+Affect on Disease Symptoms+Severity

Viruses infect specific cells by binding viral surface proteins to specific receptors on host cells.

Example: HIV gp120 binds to the CD4 receptor on T cells.

The type of cell infected determines the symptoms and disease:

• Rabies → neurons → encephalitis

• Hepatitis B → hepatocytes → hepatitis

Viruses use normal cell receptors to enter cells and replicate.

Cell Death-Caused Viral Disease Signs+Symptoms

• Cell death: Viruses often inhibit host protein synthesis while allowing viral proteins to be made. Apoptosis can also cause cell death through caspase activation.

• Inclusion bodies: Viral proteins/particles can form visible inclusions inside cells.

  • Negri bodies → rabies

  • Owl’s eye inclusions → CMV

• Cell fusion: Some viruses cause infected cells to fuse, forming multinucleated giant cells, especially herpesviruses and paramyxoviruses.

• Cytopathic effect (CPE): Infected cells change appearance, typically becoming round and dark, followed by cell lysis or giant-cell formation. CPE helps detect and measure viruses in the laboratory.

• Malignant transformation: Some viruses cause uncontrolled cell growth and prolonged survival, contributing to cancer.

• No visible effect: Some viruses can replicate without causing obvious changes, allowing the cell to survive and continue functioning.

Virus Host Defense Evasion Methods

Viruses use immune evasion to avoid being destroyed by the immune system.

• Block immune signals: Viruses make cytokine decoys that bind and block immune mediators like IL-1 and TNF.

• Reduce MHC I: This makes infected cells harder for cytotoxic T cells (CTLs) to recognize and kill.

• Block interferon: Viruses can prevent interferon production or interfere with its antiviral effects.

• Avoid NK cells: Some viruses prevent infected cells from being recognized by natural killer (NK) cells.

• Glycan shield: Surface sugars can hide viral antigens from antibodies.

• Multiple serotypes: Some viruses have many antigenic types, so immunity to one type may not protect against another.

  • Rhinovirus: >100 serotypes → contributes to frequent common colds.

  • Influenza, HIV, HCV, SARS-CoV-2: multiple antigenic types → makes vaccination and long-term immunity more difficult.

TABLE 32–4Important Mechanisms by Which Viruses Evade Host Defenses

Host Defense Affected	Mechanism of Evasion	Virus That Employs the Mechanism
Cytotoxic T cells	Reduces MHC class I proteins, thereby decreasing killing by cytotoxic T cells	HIV, HSV, CMV, adenovirus
Helper (Th-1) T cells	Blocks IL-12, which reduces formation of Th-1 cells, thereby decreasing cell-mediated immunity	Measles virus
Interferon	Blocks synthesis of interferon by virus-infected cells	EBV, HCV, SARS-CoV-2
Interferon	Blocks synthesis of kinase that phosphorylates initiation factor-2	HIV, influenza, and HSV
Interferon	NS1 protein blocks action of protein kinase and ribonuclease that inhibit viral replication	Influenza
Interferon	Blocks action of protein kinase	Hepatitis C virus
Interleukins	Encodes receptors for immune mediators; receptors are secreted by infected cells, binds mediators, and inactivates them	Vaccinia virus encodes receptor for IL-1
Chemokines	Encodes chemokine receptor; this blocks action of chemokine, thereby inhibiting migration of inflammatory cells to site of infection	Vaccinia virus, CMV
Complement	Encodes protein that binds to complement protein C3b; this blocks opsonizing action of C3b as well as its ability to participate in forming the membrane attack complex	HSV
Antibody	Glycans, especially oligomannose, coat envelope proteins decreasing antibody synthesis and binding	HIV, SARS-CoV-2, HCV