Introduction to Virology

  1. STRUCTURAL COMPONENTS OF VIRUSES

a. Viral nucleic acids: The inner core contains either DNA or RNA, never both. This determines if the virus is classified as a DNA or RNA virus.

b. Viral capsid & symmetry: The capsid is a protective protein coat made of repeating subunits called capsomeres. It protects the genome, gives the virus its shape, and has precise geometric symmetry.

c. Viral proteins

  • Surface spikes (glycoproteins): Project from the surface, bind to specific host cell receptors, and determine host range and tissue tropism.


  • Matrix protein: A protein layer between the capsid and envelope that provides structural support and assists in assembly/budding.


  • Early proteins: Nonstructural enzymes and regulators used to replicate the genome.


  • Late proteins: Structural proteins used to build the new virions (capsid, envelope glycoproteins).


d. Viral envelope: An outer lipoprotein membrane derived from the host cell. It helps the virus enter cells and evade immune responses. It is highly fragile and easily destroyed by heat, drying, detergents, and alcohol. Not all viruses have one.

  1. COMPARE AND CONTRAST PRIONS WITH CONVENTIONAL VIRUSES (Note: No information regarding prions is available in the provided slide sources.)

  2. VIRAL REPLICATION

a. Viral growth curve Viruses are obligate intracellular parasites. The most important phase is the

ECLIPSE PERIOD: the time after a virus enters a host cell but before complete infectious virions are assembled. During the eclipse period, NO infectious virus particles can be detected inside or outside the cell.



b. Growth cycle events

i. Attachment, penetration, and uncoating (Early Events)

  • Attachment (Adsorption): Virus binds highly specific host cell receptors.

  • Penetration (Entry):

    • Enveloped viruses enter via fusion with the cell membrane or endocytosis.

      • Nonenveloped viruses enter by injecting their nucleic acid or via endocytosis.

  • Uncoating: Often triggered by low pH in the endosome, causing vesicle rupture or fusion, which releases the infectious viral genome into the cytoplasm.


ii. Gene expression and genome replication

  • mRNA Synthesis: RNA viruses replicate in the cytoplasm.

  • DNA viruses replicate in the nucleus (Exception: Poxvirus replicates in the cytoplasm).


  • Translation: Early proteins are made first to replicate the genome. Late proteins are made next to build the new virus.


  • Release: Enveloped viruses exit quietly via budding. Nonenveloped viruses exit explosively via cell lysis/rupture.

  • VIRAL PATHOGENESIS Viral infections cause direct effects on cells including cell lysis, loss of normal cell function, cytopathic effects (CPE), and persistent or latent infections. The host immune response triggers inflammation, interferons, NK cells, and CD8 cells. This results in clinical disease presenting as fever, fatigue, myalgias, rash, and tissue injury.

  • LABORATORY IDENTIFICATION OF VIRUSES

a. Cell culture Detects live virus by looking for cytopathic effects (CPE). It confirms viable virus but is very slow (days to weeks) and some viruses do not grow well.

b. Microscopic identification Detects the virus or infected cells rapidly. Light microscopy sees viral-induced changes, while electron microscopy can see actual viral particles. It has lower sensitivity.

c. Serologic procedures Detects host antibodies (IgM/IgG) from blood to indicate recent or past infection. A fourfold increase of IgG from an acute sample to a convalescent sample (2-4 weeks later) suggests recent infection. Limitation: Antibodies take time to develop.

d. Antigen detection Detects viral proteins from swabs rapidly and inexpensively (e.g., rapid flu, COVID, RSV). It is less sensitive than PCR.

e. Nucleic acid detection (PCR/NAAT) Detects viral DNA or RNA. It is highly sensitive and specific, and detects early infection. Limitations include higher cost and specialized equipment requirements.

  1. SPECIFIC VIRAL INFECTIONS: BUZZWORDS & MUST-KNOWS

a. DNA Enveloped Viruses


i. Herpesviruses (Double-stranded DNA, replicate in nucleus, establish LATENCY)

  • HSV-1 (Cold Sores): Saliva/direct contact. Latent in Trigeminal ganglion. Causes oral herpes, keratitis, encephalitis. Diagnosed by PCR.


  • HSV-2 (Genital Herpes): Sexual/vertical transmission. Latent in Sacral ganglia. Causes painful genital vesicular lesions, neonatal herpes. Diagnosed by PCR.



  • VZV (Varicella-Zoster): Respiratory droplets. Chickenpox (pruritic, "dew drops on a rose petal" rash starting on face/trunk). Latent in Dorsal root ganglia. Shingles (burning, painful dermatomal rash).



  • EBV (Epstein-Barr): Saliva (kissing disease). Infects B cells via CD21 receptor. Activated CD8 T cells attack. Triad: Fever, pharyngitis, posterior cervical lymphadenopathy. Splenomegaly. Maculopapular rash if given ampicillin/amoxicillin. Diagnosed by rapid Monospot. Immune response.



  • CMV (Cytomegalovirus): Bodily fluids/vertical. Latent in monocytes/macrophages. Immunocompromised: Retinitis, pneumonitis. Congenital: Deafness, microcephaly, "blueberry muffin" rash, periventricular calcifications. Diagnosed by PCR.


ii. Poxviruses

  • High-yield rule: Exception to the DNA rule because it replicates in the cytoplasm. Replicate in cytoplasm.

  • No latency


  • Structure: They are enveloped, double-stranded DNA (dsDNA) viruses.

  • Shape: Large and brick-shaped.

  • Replication: They replicate in the cytoplasm, which is a notable exception to the general rule that DNA viruses replicate in the nucleus.

  • Latency: Unlike herpesviruses, poxviruses do NOT establish latency.

1. Smallpox (Variola virus)

  • Transmission: Transmitted via respiratory droplets or direct contact with skin lesions. Humans are the only natural reservoir for this virus.

  • Pathogenesis: Inhalation of respiratory droplets -> replicates in the upper respiratory tract -> spreads to lymph nodes -> primary viremia (virus in the blood) -> replicates in reticuloendothelial organs -> secondary viremia -> infects skin and mucous membranes to cause a rash.

  • Clinical Findings:

    • Primary viremia phase: High fever, malaise, headache, and backache.

    • Secondary viremia phase: Rash that progresses in stages from macules -> papules -> vesicles -> pustules -> scabs.

    • Key identifying feature: All lesions will be in the exact same stage of development at the same time.

  • Laboratory Diagnosis: PCR.


2. Mpox (formerly Monkeypox)

  • Transmission: Transmitted through direct skin-to-skin contact with lesions.

  • Pathogenesis: The virus enters through broken skin or mucous membranes -> viral replication -> spreads to lymph nodes -> primary viremia -> spreads to the skin and mucous membranes.

  • Clinical Findings:

    • Fever, chills, and myalgias.

    • Lymphadenopathy (swollen lymph nodes in the cervical, axillary, and inguinal regions).

    • Vesiculopustular rash.


3. Molluscum Contagiosum Virus (MCV)

  • Transmission: Direct skin-to-skin contact, sexual contact, autoinoculation, swimming pools, and fomites like shared towels, clothing, or gym equipment.

  • Pathogenesis: The virus enters through tiny breaks in the skin -> replicates in epidermal keratinocytes -> causes a localized proliferation of infectious skin cells.

  • Clinical Findings:

    • Usually painless and asymptomatic.

    • Presents as small (2-5 mm), smooth, flesh-colored or pearly, dome-shaped papules.

    • Key identifying feature: Central umbilication (a dimple in the middle of the papule).

    • Common locations: Face, trunk, arms, and legs in children; genital area, lower abdomen, and inner thighs in adults.

  • Laboratory Diagnosis: Clinical diagnosis based on the distinct appearance of the papules




b. DNA Non-Enveloped Viruses i. Adenoviruses ii. Papillomaviruses iii. Parvoviruses (Note: No clinical, transmission, or pathogenesis data for these three are present in the provided slides).



b. DNA Non-Enveloped Viruses

i. Adenoviruses

  • Structure: Double-stranded DNA (dsDNA).

  • Transmission: Respiratory droplets, fecal-oral, swimming pools, fomites.

  • Pathogenesis: Infects epithelial cells (respiratory tract, conjunctiva, GI tract, urinary tract) causing cell lysis and inflammation.

  • Clinical Findings:

    • Classic Triad: Fever, pharyngitis, conjunctivitis (Pharyngoconjunctival fever).

    • GI: Nausea, vomiting, diarrhea (NVD).

    • GU: Hemorrhagic cystitis (peeing blood)

  • Laboratory Diagnosis: PCR.

  • High-Yield Pearls: Outbreaks common in military recruits and dormitories; causes hemorrhagic cystitis in children.


ii. Papillomaviruses (HPV)

  • Structure: Double-stranded DNA (dsDNA).

  • Transmission: Direct skin-to-skin contact, sexual contact, vertical transmission.

  • Pathogenesis & Clinical Findings: Virus enters through microabrasions and infects the squamous epithelium.

    • Low-Risk Strains (HPV 6 & 11): Infects basal cells but does NOT integrate into host DNA (non-oncogenic).

      • Clinical: Genital warts (condyloma acuminata) and laryngeal papillomas.


    • High-Risk Strains (HPV 16 & 18): Infects basal keratinocytes and integrates into host chromosomes, causing continuous overproduction of viral proteins (oncogenic).

      • Clinical: Cervical cancer, anogenital cancer, and oropharyngeal cancer.

  • Laboratory Diagnosis:

    • Low-risk: Clinical diagnosis.

    • High-risk: Smear, biopsy, and HPV DNA testing.


iii. Parvoviruses (Parvovirus B19)

  • Structure: Single-stranded DNA (ssDNA). High-Yield Pearl: This is the ONLY human ssDNA virus.

  • Transmission: Respiratory droplets, vertical transmission.

  • Pathogenesis: Inhalation -> viremia -> bone marrow -> attaches to the P antigen on erythroid precursor cells -> viral replication -> cell lysis and destruction of RBC precursors. This causes a temporary cessation of RBC production (transient aplastic state for 7-10 days).

  • Clinical Findings:

    • Healthy child: Fifth disease (Erythema infectiosum). Presents with an immune-mediated "slapped cheek" rash and a lacy rash on the trunk and extremities.

    • Pregnant patients: Infects fetal erythroid precursors, causing severe fetal anemia, hydrops fetalis, high output heart failure, and fetal demise.

    • Adults: Immune-mediated polyarthralgia and arthritis.

    • Other: Can cause an aplastic crisis.

  • Laboratory Diagnosis: IgM serology for acute infection. PCR is used if the patient is immunocompromised or in an aplastic crisis.



c. RNA Enveloped Viruses

i. Orthomyxoviruses (Influenza A, B, C)

  • Structure & Pathogenesis: Single-stranded RNA (ssRNA). High-Yield Exception: It replicates in the nucleus. It uses Hemagglutinin to bind to sialic acid on host cells for entry, and uses Neuraminidase to cleave and release newly formed virions.

  • Clinical Findings: Abrupt onset of high fever and myalgias.

  • Laboratory Diagnosis: PCR, rapid antigen test.

ii. Paramyxoviruses

  • Structure & Pathogenesis: ssRNA, replicates in the cytoplasm. Uses a Fusion (F) protein to cause host cells to merge into multinucleated giant cells (syncytia).

  • Specific Viruses & Clinical Findings:

    • Respiratory Syncytial Virus (RSV): Primarily affects infants. Infects the lower respiratory tract causing bronchiolitis (wheezing, tachypnea, crackles). Diagnosis: PCR, syncytia visible on microscopy.

    • Parainfluenza: Causes Croup (laryngotracheobronchitis). Presents with a barking cough, inspiratory stridor, and a classic "steeple sign" on a neck X-ray. Diagnosis: Clinical, PCR.

    • Measles (Rubeola): Airborne transmission (highly contagious). Presents with the 3 C's (Cough, Coryza, Conjunctivitis), Koplik spots (white spots inside the mouth), and a descending deep red maculopapular rash. Complication: Subacute sclerosing panencephalitis (SSPE) years later. Diagnosis: PCR, clinical.

    • Mumps: Transmitted via respiratory droplets/saliva. Viremia leads to painful parotid gland swelling. Complications: Orchitis, aseptic meningitis, pancreatitis. Diagnosis: PCR, serology.

iii. Coronaviruses

  • Pathogenesis: Uses its Spike (S) protein to bind to ACE2 receptors on host cells.

  • Clinical Findings: Mild disease presents with a loss of taste or smell. Severe disease can progress to dyspnea and Acute Respiratory Distress Syndrome (ARDS).

  • Laboratory Diagnosis: PCR.



iv. Togaviruses (Rubella)

  • Transmission: Respiratory droplets or vertical transmission (mother to fetus).

  • Clinical Findings (Acquired): Fine pink descending rash, prominent posterior auricular and suboccipital lymphadenopathy, and arthralgias (especially in adults).

  • Clinical Findings (Congenital Rubella Syndrome): Classic triad of cataracts, patent ductus arteriosus (PDA/heart defect), and deafness.

  • Laboratory Diagnosis: PCR, serology.



v. Rhabdoviruses (Rabies lyssavirus)

  • Structure: Distinctive bullet-shaped capsid.

  • Transmission: Animal bites (via saliva) or exposure to bats (aerosolized).

  • Pathogenesis: Virus enters peripheral nerves, travels via retrograde axonal transport to the CNS, replicates, and then travels back down to the salivary glands.

  • Clinical Findings: Presents as either Furious rabies (hydrophobia, seizures) or Dumb rabies (paralysis).

  • Laboratory Diagnosis: Presence of Negri bodies in neurons on histology; PCR.


vi. Retroviruses (HIV)

  • Structure & Pathogenesis: Positive-sense RNA virus. It carries the enzyme reverse transcriptase to convert its RNA genome into DNA, which then permanently integrates into the host cell's DNA as a provirus. It binds specifically to CD4 receptors.

  • Clinical Findings: Progressively destroys CD4+ T cells, causing severe immunosuppression. AIDS is diagnosed when the CD4 count drops < 200 and the patient develops opportunistic infections.

  • Laboratory Diagnosis: Serology (HIV Ab/Ag screening tests), viral load testing.

    RNA Non-Enveloped Viruses

    i. Picornaviruses

    • General Characteristics: Small, non-enveloped, single-stranded RNA (ssRNA) viruses that replicate in the cytoplasm and infect both humans and animals. Memory Trick: "PERCH" (Poliovirus, Echovirus, Rhinovirus, Coxsackievirus, Hepatitis A).

    • Poliovirus (Enterovirus):

      • Transmission: Fecal-oral, saliva, and respiratory secretions.

      • Pathogenesis: Virus enters the mouth -> replicates in the oropharynx and intestinal mucosa (tonsils and Peyer patches) -> spreads to regional lymph nodes -> primary viremia. In some cases, it enters the CNS and destroys anterior horn motor neurons of the spinal cord.

      • Clinical Findings: 90-95% of cases are asymptomatic. Can cause abortive poliomyelitis (mild fever/sore throat), aseptic meningitis, or

      • paralytic poliomyelitis characterized by the rapid onset of asymmetric flaccid paralysis.

      • Diagnosis: PCR (stool or throat).

    • Echovirus:

      • Transmission: Fecal-oral, respiratory secretions, fomites.

      • Pathogenesis: Replicates in the oropharynx/respiratory tract -> spreads to local lymph nodes -> viremia.



  • Clinical Findings: Most are asymptomatic, but can cause aseptic meningitis. Severe disease occurs in neonates and the immunocompromised, presenting as neonatal sepsis, myocarditis, encephalitis, or hepatitis.

  • Diagnosis: PCR.


  • Rhinovirus:

    • Transmission: Respiratory droplets and fomites; most common in Fall and Spring.

    • Pathogenesis: Binds to ICAM-1 receptors on respiratory epithelial cells -> replicates -> localized upper airway inflammatory response.


    • Clinical Findings: The common cold.

    • Diagnosis: Clinical diagnosis; PCR.


  • Coxsackievirus:

    • Transmission: Fecal-oral, respiratory droplets; most common in Summer and early Fall.

    • Pathogenesis: Replicates in oropharynx and intestinal mucosa -> regional lymph nodes -> viremia.

    • Clinical Findings:

      • Type A: Causes Hand-Foot-Mouth disease (painful oral ulcers and a vesicular rash on hands and feet) and Herpangina (painful vesicles and ulcers on the soft palate and posterior pharynx).

      • Type B: Causes myocarditis, pericarditis, and pleurodynia (chest pain/arrhythmias).

    • Diagnosis: PCR.



  • Hepatitis A Virus:

    • Transmission: Fecal-oral, contaminated food/water, close personal contact.

    • Pathogenesis: Replicates in GI tract -> viremia -> travels to the liver and replicates in hepatocytes/Kupffer cells -> causes immune-mediated liver injury via CD8+ T cells -> secreted in bile/feces. High-Yield Pearl: There is no chronic or carrier state.


    • Clinical Findings: Acute hepatitis. Prodromal phase: RUQ discomfort, N/V, fever, anorexia. Icteric phase: Jaundice, pruritus, pale/clay-colored stool, hepatomegaly. Children are often asymptomatic.

    • Diagnosis: Serology looking for IgM antibodies.

  • ii. Caliciviruses (Norovirus)

    • Structure: ssRNA.

    • Transmission: Fecal-oral route, person-to-person, fomites. It is highly contagious due to a very low infectious dose. Common food sources include leafy greens, fresh fruit, and shellfish.

    • Pathogenesis: Infects intestinal enterocytes causing villous blunting, brush border dysfunction, and decreased absorption.

    • Clinical Findings: Vomiting outbreaks (often associated with cruise ships), sudden onset profuse vomiting, nausea, watery diarrhea, and abdominal cramping.

    • Diagnosis: PCR of stool sample.




    iii. Reoviruses (Rotavirus)

    • Structure: Double-stranded RNA (dsRNA).

    • Transmission: Fecal-oral route and fomites. Outbreaks are highly associated with daycare centers.

    • Pathogenesis: Ingested virus infects mature enterocytes of the small intestine. It produces a viral protein called NSP4 that acts as an enterotoxin, leading to profuse watery diarrhea and vomiting.

    • Clinical Findings: Most common cause of severe diarrhea in infants and children worldwide. Presents with profuse watery diarrhea, vomiting, fever, abdominal cramping, and dehydration.

    • Diagnosis: PCR (stool) or rapid stool antigen test