NURS1206 Virology and Viral Replication Study Notes

General Characteristics of Viruses

  • Viruses are defined as obligate intracellular parasites and acellular infectious agents.

  • They require the presence of a host cell in order to multiply.

  • Unique characteristics include:

    • They are "floating" entities.

    • They possess a protein shell known as a capsid.

    • They contain a genome consisting of either DNA or RNA.

    • Viral replication occurs when the virus takes control of the host's cellular functions.

Viral Classification Criteria

Viruses are categorized based on four primary attributes:

  1. Type of nucleic acid (DNA or RNA).

  2. Presence or absence of a protein capsid.

  3. Presence or absence of a lipid envelope.

  4. Physical size.

Nucleic Acid Composition and Orientation

  • Viruses are classified as either DNA or RNA viruses.

  • Nucleic acid sequences can encode various quantities of information, ranging from a simple message to hundreds of enzymes and structural proteins.

  • RNA Virus configurations:

    • Positive (+) strand.

    • Negative (-) strand.

  • DNA Virus configurations:

    • Positive (+) and Negative (-) strands.

Viral Replication Processes and Pathways

  • Positive (+) RNA Viruses:

    • These are the equivalent of preformed messenger RNA (mRNA).

    • Upon invading a cell, they are immediately ready for translation.

    • They utilize host cell ribosomal proteins and enzymes to translate the positive RNA into an RNA-dependent RNA polymerase, which then creates negative-stranded copies of the RNA for replication.

    • Pathway: Positive (+) RNA $\rightarrow$ Translation $\rightarrow$ Structural Proteins and Enzymes.

  • Negative (-) RNA Viruses:

    • These viruses cannot translate directly into protein.

    • They must carry a viral RNA-dependent RNA polymerase within the virion.

    • They first create a positive-strand copy of their genome, which is then translated into viral proteins.

    • Pathway: Negative (-) RNA $\xrightarrow{\text{Transcription with virus RNA-dependent RNA polymerase}}$ Positive (+) RNA (mRNA) $\rightarrow$ Translation $\rightarrow$ Structural Proteins and Enzymes.

  • Retroviruses:

    • Pathway: RNA $\xrightarrow{\text{Reverse Transcription}}$ DNA $\xrightarrow{\text{Transcription}}$ mRNA $\xrightarrow{\text{Translation}}$ Structural Proteins and Enzymes.

  • DNA Viruses:

    • Generally more genetically complex than RNA viruses.

    • Viral transcription is categorized into three stages: immediate early, early, and late transcription.

    • DNA segments are transcribed in the nucleus into mRNA, spliced/processed, and moved to the cytoplasm for translation.

    • Pathway: DNA $\xrightarrow{\text{Transcription}}$ mRNA $\xrightarrow{\text{Translation}}$ Structural Proteins and Enzymes.

Virus Size and Comparative Dimensions

Viruses are compared to bacteria and other agents in terms of size:

  • DNA Viruses:

    • Parvoviridae: 22 nm22\,nm

    • Hepadnaviridae: 42 nm42\,nm

    • Papovaviridae: 50 nm50\,nm

    • Adenoviridae: 80 nm80\,nm

    • Herpesviridae: 150 nm150\,nm

    • Poxviridae: 250 nm250\,nm

  • RNA Viruses:

    • Picornaviridae: 27 nm27\,nm

    • Caliciviridae: 30 nm30\,nm

    • Reoviridae: 60 nm60\,nm

    • Togaviridae: 70 nm70\,nm

    • Orthomyxoviridae: 100 nm100\,nm

    • Coronaviridae: 120 nm120\,nm

    • Retroviridae: 120 nm120\,nm

    • Paramyxoviridae: 150 nm150\,nm

    • Rhabdoviridae: 70 nm×170 nm70\,nm \times 170\,nm

  • Comparative Agents:

    • Mycoplasma pneumoniae: 150 nm150\,nm

    • Chlamydia: 400 nm400\,nm

    • Rickettsia: 500 nm500\,nm

    • Escherichia coli is significantly larger.

Structural Components: Capsid and Envelope

  • Capsid:

    • Function: Protects the nucleic acid from the environment.

    • Shape: Varies by virus.

      • Icosahedral: Found in both RNA and DNA viruses.

      • Helical: Found in RNA viruses only.

  • Envelope:

    • A lipid bilayer membrane that provides additional protection.

    • Acquired via "budding" through the host cell membrane, tearing off a piece of the membrane upon exit.

    • Virulence correlation:

      • Enveloped viruses: Generally less virulent.General Characteristics of Viruses

        Viruses are defined as obligate intracellular parasites and acellular infectious agents.

        They require the presence of a host cell in order to multiply.

        Unique characteristics include:

        They are "floating" entities.

        They possess a protein shell known as a capsid.

        They contain a genome consisting of either DNA or RNA.

        Viral replication occurs when the virus takes control of the host's cellular functions.

        Viral Classification Criteria

        Viruses are categorized based on four primary attributes:

        Type of nucleic acid (DNA or RNA).

        Presence or absence of a protein capsid.

        Presence or absence of a lipid envelope.

      • Naked (non-enveloped) viruses: Generally more virulent.

The Viral Replication Cycle

Viruses cannot reproduce independently; they must hijack a host cell's machinery.

  1. Adsorption and Penetration: The viral particle binds to the host cell membrane. Unlike bacteriophages that inject DNA, these viruses are fully internalized (capsid and nucleic acid) via endocytosis or membrane fusion.

  2. Uncoating of the Virus: The nucleic acid is released from the capsid into either the host cell's nucleus or cytoplasm.

  3. Synthesis and Assembly: The machinery builds enzymes and structural proteins, and the genetic material is copied. RNA or DNA and proteins assemble into intact helical or icosahedral viruses.

  4. Release of Virions:

    • Naked viruses: Released via cell lysis (death) or exocytosis.

    • Enveloped viruses: Acquire their envelope by budding through the Golgi apparatus, nuclear membrane, or cytoplasmic membrane.

Host Cell Outcomes Following Infection

  • Cell Death: Host function shuts down completely as the cell is commandeered for replication, leading to death.

  • Transformation: Infection activates or introduces oncogenes, leading to uncontrolled and uninhibited cell growth (cancer).

  • Latent Infection: The virus remains in a "sleeping state," surviving without producing an overt clinical infection. Reactivation can occur due to various factors.

  • Chronic Slow Infection: Disease manifests only after decades of indolent (slow-moving) infection.

DNA Virus Families and Classification

Most DNA viruses are double-stranded, show icosahedral symmetry, and replicate in the host nucleus.

  • Families:

    1. Herpesviridae

    2. Hepadnaviridae

    3. Adenoviridae

    4. Papovaviridae

    5. Parvoviridae

    6. Poxviridae

  • Rule Breakers:

    • Parvoviridae: Has only one strand (single-stranded).

    • Poxviridae: Has double-helix DNA but lacks standard icosahedral symmetry (Complex "Pox in a box" shape).

  • Structural Classifications:

    • Enveloped DNA Viruses: Herpesviridae, Hepadnaviridae, Poxviridae.

    • Naked DNA Viruses: Papovaviridae, Adenoviridae, Parvoviridae.

RNA Virus Families and Classification

RNA viruses are characterized as single-stranded (half positive, half negative), enveloped, having helical symmetry, and replicating in the cytoplasm.

  • Families:

    1. Picornaviridae

    2. Caliciviridae

    3. Togaviridae

    4. Flaviviridae

    5. Coronaviridae

    6. Retroviridae

    7. Bunyaviridae

    8. Orthomyxoviridae

    9. Paramyxoviridae

    10. Rhabdoviridae (Bullet-shaped)

    11. Arenaviridae

    12. Filoviridae

    13. Reoviridae

  • Taxonomy by Genome:

    • Positive-Stranded (+) Naked: Picornaviridae, Caliciviridae.

    • Positive-Stranded (+) Enveloped: Togaviridae, Flaviviridae, Coronaviridae, Retroviridae.

    • Negative-Stranded (-) Enveloped: Bunyaviridae, Orthomyxoviridae, Paramyxoviridae, Rhabdoviridae, Arenaviridae, Filoviridae.

    • Double-Stranded Naked: Reoviridae.

Picornaviridae

  • Small, icosahedral viruses with single-stranded positive RNA.

  • Enterovirus:

    • Infects intestinal epithelial and lymphoid cells.

    • Transmitted via the fecal-oral route; excreted in feces.

    • Poliovirus: Initially replicates in tonsils and Peyer's patches. Spreads to blood and across the blood-CNS barrier to the spinal cord. Can cause paralytic disease ranging from localized paralysis to quadriplegia and respiratory muscle dysfunction. Vaccines: Oral Polio Vaccine (OPV) and Intravenous Polio Vaccine.

    • Coxsackie Virus: Infants and young children are most susceptible.

      • Coxsackie A: Causes Herpangina and Hand, Foot, and Mouth Disease.

      • Coxsackie B: Causes pleurodynia and myocarditis/pericarditis.

      • Treatment: No definite treatment or vaccine.

  • Rhinovirus:

    • Causes the "common cold."

    • Transmitted via aerosols (small/large particle) or direct contact.

    • Symptoms typically last 7−147-14 days.

Coronaviridae

  • Enveloped single-stranded RNA virus with large club- or petal-shaped surface projections.

  • SARS (Severe Acute Respiratory Syndrome):

    • First Pandemic of the 21st Century; originated from bats.

    • Symptoms: High fever, headache, malaise, body aches, dry cough.

    • Transmission: Airborne and droplets.

  • MERS-CoV (Middle East Respiratory Syndrome):

    • First reported in Saudi Arabia and Jordan in 2012.

    • Origin: Camels.

    • Symptoms: Fever, cough, shortness of breath, diarrhea.

  • SARS-CoV-2 (COVID-19):

    • Origin: Bats in Wuhan, 2019.

    • Transmission: Respiratory liquid particles from coughing, sneezing, speaking, etc.

    • Detection: RT PCR and Antigen Tests.

    • Quarantine Protocols (Vaccinated with 2 boosters):

      • Mild/Moderate: 55 days.

      • Critical: 77 days.

      • No boosters (All cases): 77 days.

    • Global Impact: 766,440,796766,440,796 confirmed cases; 6,932,5916,932,591 deaths.

    • Philippine Impact: 4,119,5164,119,516 confirmed cases; 66,45366,453 deaths.

Orthomyxoviridae (Influenza)

  • Spread via small particle respiratory aerosols.

  • Structure: 8 segments of negative-stranded RNA in a helical capsid, surrounded by an outer membrane with glycoprotein spikes.

  • Glycoproteins:

    • Hemagglutinin (HA): Attaches to host sialic acid receptors.

    • Neuraminidase (NA): Cleaves neuraminic acid to disrupt the mucin barrier.

  • Antigenic Variation:

    • Antigenic Drift: Small changes in HA and NA causing seasonal epidemics.

    • Antigenic Shift: Major changes in HA and NA causing global pandemics.

  • Pandemic History:

    • 18891889: H2N2

    • 19011901: H3N8

    • 19181918: H1N1 (Spanish Flu)

    • 19471947: H1N1

    • 19571957: H2N2 (Asian Flu)

    • 19681968: H3N2 (Hong Kong Flu)

    • 19771977: H1N1

    • 19971997: H5N1 (Bird Flu)

    • 20092009: H1N1

  • Cold vs. Flu Symptoms:

    • Onset: Gradual (Cold) vs. Abrupt (Flu).

    • Fever: Rare (Cold) vs. Usual (Flu).

    • Aches/Chills: Slight/Uncommon (Cold) vs. Usual (Flu).

    • Fatigue: Sometimes (Cold) vs. Usual (Flu).

    • Stuffy Nose/Sore Throat/Sneezing: Common (Cold) vs. Sometimes (Flu).

  • Treatment: Oseltamivir and vaccines.

Togaviridae

  • Small, enveloped, single-stranded positive RNA.

  • Alpha Virus (Chikungunya):

    • Mosquito-borne (Aedes aegypti and Aedes albopictus).

    • Symptoms: Fever, rash, joint pain/swelling.

    • No encephalitis.

  • Rubivirus (Rubella/German Measles):

    • Causes Congenital Rubella (affects heart, eyes, CNS).

    • Symptoms: Fever, lymphadenopathy, rash spreading from forehead downward.

Flaviviridae

  • Enveloped viruses with single-strand positive RNA.

  • Yellow Fever Virus: Transmitted by Aedes aegypti. Symptoms include jaundice, fever, and backache. 90% of cases are in Africa.

  • Dengue Virus: "Break-bone Fever." 4 serotypes.

    • Symptoms: High fever, body aches, rash.

    • Diagnosis: Dengue NS1, IgG, and IgM tests.

    • IgM(+)/IgG(-): Current infection.

    • IgM(-)/IgG(+): Past infection.

    • Dengvaxia used for prevention.

  • Zika Virus: Transmitted by Aedes mosquitos. Causes microcephaly in fetuses.

Paramyxoviridae

  • Single RNA (-) strand, F protein, and a single glycoprotein spike for HA/NA.

  • Respiratory Syncytial Virus (RSV): Leading cause of pneumonia in children under 66 months; forms syncytial cells.

  • Mumps Virus: Replicates in upper respiratory tract; infects the parotid gland and testes (orchitis).

  • Measles Virus (Rubeola):

    • Highly contagious via nasopharyngeal secretions.

    • Symptoms: High fever (41∘C41^{\circ}C), Koplik's Spots (blue-white centers on red base), rash spreading forehead to feet.

    • Timeline: 1010-day incubation, 3-43\text{-}4 day prodrome, 66 days of rash.

Rhabdoviridae (Rabies)

  • Bullet-shaped, enveloped RNA virus.

  • Infects all warm-blooded animals (reservoirs: dogs, skunks, bats, etc.).

  • Pathology: Replicates at the wound site, migrates to CNS, causing fatal encephalitis.

  • Symptoms: Hydrophobia (painful pharyngeal contractions when swallowing), hyperactivity, agitation.

  • Diagnostic Marker: Negri Bodies (oval inclusions in brain cell cytoplasm).

  • Vaccination:

    • Animals: 1 dose at 33 months old with yearly booster.

    • Prophylactic (Humans at risk): 2 doses.

    • Post-exposure: 1 dose Human Rabies Immunoglobulin + 5 doses Rabies Vaccine.

Filoviridae and Arenaviridae

  • Filoviridae: Ebola and Marburg.

    • Ebola causes clotting issues and internal bleeding; transmitted via body fluids.

    • Marburg: Fever, myalgia, progressing to jaundice and multi-organ failure. Outbreak in Equatorial Guinea (Feb 2023).

  • Arenaviridae: Causes South American Hemorrhagic Fevers (Junin, Machupo, Guanarito, Sabia).

Viral Hepatitis

General symptoms: Fatigue, fever, muscle aches, followed by jaundice after 1-21\text{-}2 weeks.

  • Hepatitis A (HAV): Naked, +RNA, Picornaviridae. Fecal-oral route. 15-4015\text{-}40 day incubation. Anti-HAV IgG provides lifelong protection.

  • Hepatitis B (HBV): Enveloped, circular double-stranded DNA, Hepadnaviridae ("Dane Particle").

    • Antigens:

      • HBsAg: Indicates live virus/infection.

      • HBcAg: Determines new vs. old infection.

      • HbeAg: Indicates high infectivity.

  • Hepatitis C (HCV): Enveloped +RNA, Flaviviridae. 85% become chronic; 20% lead to cirrhosis. Treated with Ribavirin.

  • Hepatitis D (HDV): Single-stranded negative RNA, Deltaviridae. Requires HBV for replication. High mortality (5-15%5\text{-}15\%).

  • Hepatitis E (HEV): +RNA, Hepeviridae. Fecal-oral (contaminated water during monsoons).

  • Hepatitis G (HGV): RNA virus, Flaviviridae. Transfusion route; no conclusive liver disease.

Herpesviridae

  • DNA viruses that develop latent infections and are controlled by cell-mediated immunity.

  • Herpes Simplex Virus (HSV): HSV-1 and HSV-2. Causes gingivostomatitis, genital herpes, and encephalitis. Treated with Acyclovir.

  • Varicella Zoster Virus (VZV):

    • Varicella (Chickenpox): Fever and rash in children.

    • Herpes Zoster (Shingles): Reactivation in nerves causing painful lesions.

  • Cytomegalovirus (CMV): Transmitted via body fluids. Causes congenital disease and retinitis. Treated with Valganciclovir.

  • Epstein-Barr Virus (EBV): Transmitted via saliva. Causes Mononucleosis and Burkitt's Lymphoma.

Additional DNA Viruses

  • Poxviridae: Replicates in the cytoplasm. Includes Smallpox (last case in 1977).

  • Papovaviridae: Circular naked DNA.

    • Papilloma Virus (HPV): Causes warts and cervical cancer (strains 16 and 18). Vaccine has 98%98\% efficacy.

    • Polyomavirus: Attacks immunocompromised hosts.

  • Adenoviridae: Naked icosahedral. Causes 10%10\% of childhood URTI (rhinitis, conjunctivitis, sore throat).

  • Parvoviridae: Smallest icosahedral virus, single-stranded DNA. Causes Fifth Disease (Erythema Infectiosum) characterized by a "slapped face" rash.