HPV and Cervical Cancer Quiz

MABS Microbiology

• Virology, Respiratory, Hepatitis, Papilloma and Polyoma Viruses, Human Retroviruses are covered
• Course instructional objectives are outlined for each subject

Course Instructional Objectives

• Mcro 3.1: Describes the taxonomy, structure, function, transmission, pathogenesis, stages of viral infection, viral gene expression, viral replication, and effects at the cellular level or human immune response for Coronaviruses.
• Mcro 3.2: Describes the taxonomy, structure, function, transmission, pathogenesis, stages of viral infection, viral gene expression, viral replication and effects at the cellular level, human immune response and treatment for influenza viruses.
• Mcro 3.3: Describes the taxonomy, structure, function, transmission, pathogenesis, effects on cellular level, and human immune response for RSV, Paramyxoviridae
• Mcro 3.4: Describes the taxonomy, structure, function, transmission, pathogenesis, stages of viral infection, viral gene expression, viral replication, and effects at the cellular level or human immune response for Adenovirdae
• Mcro 3.5: Describes the taxonomy, structure, function of retroviruses (especially HIV-1), including transmission, pathogenesis, stages of viral infection, viral gene expression, viral replication, effects at the cellular level, human immune response and/or treatment.
• Mcro 3.6: Describes the taxonomy, structure, and function of Papillomaviridae, including transmission, pathogenesis, stages of viral infection, viral gene expression, viral replication, effects at the cellular level and which HPV forms are more/less likely to cause cancer.
• Mcro 3.7: Describes the taxonomy, structure, and function of hepatitis viruses (specifically HVA, HVB, and HVC), including transmission, pathogenesis, and effects on the cellular level or human immune response.

Review: Components of a Virus

• Viral Component: Nucleic acid, Capsid, Structural proteins, Non-structural proteins, Envelope
• Role in Viral Life Cycle: Encodes information for progeny virions, protein shell protecting viral nucleic acid, forms capsid and packages the genome, attachment proteins, required for replication or disease progression, lipid bilayer facilitating attachment and host cell membrane penetration
• Examples: DNA/RNA, icosahedral/helical, Matrix/Nucleocapsid, Polymerase/Helicase,Lipid bilayer

Respiratory Viruses

• Respiratory disease accounts for 75-80% of acute morbidity in the US
• Most respiratory illnesses are estimated at 80% caused by viruses: including incubation periods from 1-14 days.
• Common respiratory illnesses include: Parainfluenza viruses, influenza viruses, respiratory syncytial virus (RSV), coronaviruses (including COVID-19), adenoviruses, rhinoviruses, human metapneumovirus (hMPV), and bocaviruses.
• Average per person = 3-4 episodes annually

VAP and Cell Receptor Pairs

• Overview of various viruses, their families, structure, and associated receptors, and cell tropism
• Viruses, families, VAP, receptor, and cell tropism are listed (e.g., HIV-1, Retroviridae, gp120/CD4, T-cells, macs)

Summary: Coronaviruses

• Coronaviruses are the largest RNA viruses.
• Genome is positive sense RNA, helical nucleocapsid, and a lipid bilayer envelope containing viral spike protein (S), membrane glycoprotein, and envelope glycoprotein.
• Viral replication in the cytoplasm
• Three novel human coronaviruses causing Severe Acute Respiratory Syndrome (SARS-CoV-1, MERS-CoV, and SARS-CoV-2) in 2019 (COVID-19).
• Transmission by respiratory droplets, spikes,ACE-2 receptor.

Respiratory Epithelium

• Explains the structure and function of upper and lower respiratory tract epithelium, specifically the role in cleaning air, mucus production, trapping debris, and facilitating gas exchange.

Severe Acute Respiratory Syndrome (SARS) Viruses

• Caused by zoonotic coronaviruses
• Spread commonly by respiratory droplets
• Virus infects and destroys respiratory epithelial cells
• Causes atypical pneumonia, high fever, chills, headache, dizziness, shortness of breath, and diarrhea.
• Mortality rate is age-related variations
• Immune-mediated cytokine storm

Review: Viral Infection and the Immune System

• Describes the general viral infection process and the immune system's response.

Immune System & Coronaviruses

• High leukocytes recruitment, especially CD8 cytotoxic T cells, monocytes and neutrophils
• Cell-mediated immunity helps control infection
• Damage caused by COVID-19, both viral and immune-mediated.
• Inflammation in lung, alveolar epithelial cells, vascular endothelial cells

Summary: Influenza

• Influenza viruses belong to Orthomyxoviridae family, enveloped, pleomorphic, helical, single-stranded RNA virus, segmented.
• Classified into 3 types: A, B, and C based on antigenic variation. Influenza A causes more severe & extensive epidemics than B or C.
• Two virus-specific glycoproteins, hemagglutinin (HA), and neuraminidase (NA). These are crucial proteins for virus infection & their function.
• An important note, influenza B viruses are relatively stable.

Influenza Virus

• Family Orthomyxoviridae, linear ssRNA genome, enveloped, helical capsid
• Transmission: respiratory droplets,
• Tropism: respiratory epithelium.
• Major surface glycoproteins-hemagglutinin (HA), which binds to sialic acid glycoprotein receptor on host cell, and neuraminidase (NA), which is required for viral release in the host.
• There are 18 subtypes and 11 subtypes in human influenza virus.

Influenza, Transcription & Replication

• Overview of the influenza A virus replication cycle and the role of the virus's RNA-dependent RNA polymerase (RdRp) in transcription ,replication, & assembly.
• Influenza A viruses replicate within the nucleus, using viral mRNA & the host cell's mechanisms.

Pathogenicity & Virulence

• Pathogenicity: the ability of a microbial species to cause disease
• Virulence: the ability of a microbial strain to cause disease

Antigenic Drift vs Antigenic Shift

• Antigenic drift refers to the gradual accumulation of mutations in the influenza virus; which causes minor changes to the Hemagglutinin & Neuraminidase spike proteins.
• Antigenic shift refers to the abrupt change in the influenza virus due to reassortment of genome segments.

Influenza Virus (Features)

• Influenza structure (and components e.g. glycoproteins, hemagglutinin spikes (HA) & neuraminidase spikes (NA))
• Antigenic sites, which are binding sites on the surface proteins (HA and NA), that are targeted by antibodies after infection or vaccine.
• Antibodies that recognize & bind these sites help neutralize the virus.

Influenza Life Cycle

• Explains step by step the replication cycle of influenza virus within the host cell
• Describes how the virus makes copies of itself, transcribes itself to prepare for translation, translates viral proteins, pack the DNA, then buds from the cytoplasm leaving the cell.

Influenza Disease

• Disease symptoms, complications and treatment
• The severity of the symptoms depends on the patient’s immune status, underlying medical conditions, and the specific influenza strain.
• Common symptoms include fever, cough, sore throat, muscle aches, and fatigue; and complications from severe disease, including pneumonia, and death.

Immune System & Influenza

• Interferon release from natural killer cells & macrophages, and cytotoxic T cell responses.
• Antibody-mediated immunity also, antibodies to hemagglutinin or neuraminidase.
• Antibody-mediated immunity which develops over a few days from the body's response to infection.
• The influenza virus will damage the tissue creating a chance for a secondary (bacterial) respiratory infection.

Influenza Treatment & Prevention

• Methods used to treat and prevent influenza infection
• Symptomatic treatments e.g., Antihistamines , Acetominaphen,
• Inhibiting attachment (e.g. antibodies elicited by vaccines),
• Inhibiting viral uncoating (e.g, amantadine or rimantadine),
• Inhibiting viral release (e.g. zanamivir, or oseltamivir, and peramivir).
• Prevention: Vaccination

Classification of RNA Viruses

• Discusses the classification scheme for RNA viruses based on genome structure and capsid features.

Paramyxoviridae

• Respiratory syncytial virus (RSV) belongs to Paramyxoviridae family.
• Enveloped, helical, negative-sense linear RNA virus.
• Its name & derivation from the ability to produce cell fusion in tissue culture (syncytium formation).
• Primarily infects the bronchi, bronchioles, and alveoli of the lung.
• RSV infection occurs through respiratory route (infective secretions). A 4-6 day incubation.

Respiratory Syncytial Virus (RSV)

• Viral attachment proteins – G and F glycoproteins.
• Tropism for respiratory epithelium.
• Transmission – large droplets & direct contact.
• Common in infants (and children aged 0-2).
• High risk populations (premature infants, elderly, and transplant recipients)

VAP and Cell Receptor Pairs

• Overview and more detailed descriptions of different Viruses, families, VAPs, and respective receptors along with the cell tropism.

Classification of DNA Viruses

• DNA viruses are part of the HHAPPPPY classification system used for further grouping; including Hepadnaviridae, Herpesviridae, Adenoviridae, Parvoviridae, Poxviridae, Papillomaviridae & Polyomaviridae.
• DNA viruses have double-stranded genomes, except Parvoviridae which have single-stranded genomes.

Human Papillomavirus (HPV)

• HPV is a non-enveloped, double-stranded DNA virus that infects human genital & cutaneous tracts.
• Icosahedral outer shell
• Associated with various diseases including skin warts & cervical cancer

HPV Transformation

• HPV's oncoproteins (e.g., E5, E6, and E7) inactivating tumor suppressor proteins (e.g., p53 and Rb)
• Leads to uncontrolled cell growth & transformation.

HPV Diagnosis

• Indicates that HPV diagnosis is made through microscopy, pap smears and specific grading system.

Hepatitis Viruses

• Hepatitis refers to inflammation of the liver - caused by viruses (hepatitis A, B, C, D, and E)
• Describes the causes of Hepatitis, including viral infections, alcohol, autoimmune disorders, and ischemia

Hepatitis Overview

• Ranges from asymptomatic to self-limiting acute infection and severe acute infection to chronic infection, the features, common symptoms, and different phases of a possible disease progression

Hepatitis A Virus (HAV)

• Viral family -Picornaviridae
• Positive sense ssRNA
• Icosahedral (naked)
• Acquired through ingestion of contaminated food/water or shellfish.
• High risk populations are travelers or those in daycare settings.
• Replicates in the hepatocytes and Kupffer cells

Hepatitis C Virus (HCV)

• Viral family - Flaviviridae
• Positive sense ssRNA
• Enveloped
• Specific subtypes & geographic differences
• High mutation rate = multiple isolates
• Likely tropism is hepatocytes, potentially B cells.
• Transmission through sexual activity, or through blood transfusions, or transplantation of organs.

Hepatitis B Virus (HBV)

• Viral family - Hepadnavirus
• DNA virus
• Hepatocellular necrosis occurs due to body's immune response, not the virus.
• Transmission possible via numerous routes including transfusion, transplant recipients, mother to child, and through blood exposure