Lecture 6.2 - Viruses

Virus Classification

• Herpes virus: double-stranded DNA, enveloped
  • Types: Herpes simplex (1 and 2), Varicella zoster virus, Cytomegalovirus, Epstein Barr virus
• RNA viruses:
  • Influenza virus: single-stranded negative sense RNA, enveloped (RNA-dependent RNA polymerase)
  • Coronaviruses: single-stranded RNA, enveloped (e.g., SARS-CoV-2)
  • Polio: single-stranded RNA, non-enveloped
  • Hepatitis C: single-stranded positive sense RNA, enveloped
  • HIV: single-stranded RNA, enveloped (reverse transcriptase, integrase, and viral protease)

Virus Diagnosis

• Antigen detection: Hepatitis B
• PCR (Polymerase Chain Reaction): detect SARS-CoV-2 using primers that match a segment of the virus' genetic material
• Antibody test: HIV

Viruses and Cancer

• Human Papilloma viruses (HPV):
  • Spread by contact (touch)
  • More than 40 types can be passed on through sexual contact
  • At least a dozen types are known to cause cancer (e.g., cervical, penis, anus, vagina, vulva, mouth, and throat)
  • Vaccine widely used to prevent HPV infection in young adults
• Epstein Barr Virus (EBV):
  • Causes infectious mononucleosis ("kissing disease")
  • Passed from person to person by coughing, sneezing, or sharing drinks or eating utensils
  • Infects and stays in B lymphocytes
  • Can increase risk of developing nasopharyngeal cancer and certain lymphomas (e.g., Burkitt lymphoma)
• HIV:
  • Causes acquired immune deficiency syndrome (AIDS)
  • Increases the risk of cancer, especially those linked to other viruses (e.g., Kaposi's sarcoma - human herpesvirus 8 (HHV8))

Virus Replication

• Steps:
  • Attachment to the appropriate cells
  • Penetration of the virus into the cell (endocytosis or fusion of envelope with host cell membrane)
  • Uncoating, leading to release of the genome and other materials into the host cell
  • Production of virus-specific mRNA, resulting in the manufacture of virus components
  • Assembly of components
  • Release from target cells and further infection

Virus Structure

• Envelope: lipid bilayer - membrane acquired as the virus buds through the host cell membrane
• Capsid: protein coat for the viral genome and proteins

Virus Genome

• Types: DNA or RNA, double-stranded or single-stranded, positive or negative sense, circular or linear
• Most DNA viruses replicate in the nucleus
• Most RNA viruses replicate in the cytoplasm

DNA Viruses

• Adenoviruses: double-stranded DNA, non-enveloped
  • Causes respiratory and gastrointestinal infections, conjunctivitis
• Hepatitis B virus: partially double-stranded DNA, enveloped
  • Causes chronic hepatitis, cirrhosis, hepatocellular carcinoma

Effect on Host Cell

• Death: the cell is unable to function normally due to the virus taking over for its own multiplication
• Transformation: the cell can divide uncontrollably due to activation or introduction of oncogenes
• Latent infection: the virus remains dormant and does not cause symptoms until it is activated by some factor(s)
• Chronic infection: lasting over a period of time

RNA Virus Replication

• Occurs in the cytoplasm
• Positive sense single-stranded RNA can function as mRNA and get translated into proteins by the host ribosomes
• Negative sense RNA has to be changed to positive mRNA using the enzyme RNA-dependent RNA polymerase

DNA Virus Replication

• Occurs in the nucleus of infected cells
• Transcription and replication occur in the nucleus
• Most DNA viruses assemble in the nucleus

Antivirals

• Herpes viruses: acyclovir, famciclovir, and valacyclovir - stops viral DNA replication by inhibiting DNA polymerase
• Flu virus: Tamiflu - inhibits the neuraminidase enzyme on the surface of the virus, preventing the release of the virus
• HIV-1: triple drug therapy consisting of nucleoside reverse transcriptase inhibitors and either a non-nucleoside reverse transcriptase inhibitor, or a boosted protease inhibitor, or an integrase inhibitor

HIV Virus

• Single-stranded positive sense RNA
• Enveloped virus
• Family: retroviridae
• Genus: Lentivirus

HIV Replication

• GP120 binds to CD4 receptor and has to bind to a co-receptor
• CXCR4 on: T cells
• CCR5 on: T cells, macrophages, monocytes, and dendritic cells
• Mutation in co-receptor results in resistance to infection

Targets for HIV Therapy

• Post-attachment inhibitors
• Fusion inhibitors
• Reverse transcriptase inhibitors
• Integrase inhibitors
• Protease inhibitors

Retroviral Therapy

• Standard antiretroviral therapy (ART) consists of a combination of antiretroviral (ARV) drugs to maximally suppress the HIV virus and stop the progression of HIV disease.