Virology Notes

Baltimore Classification System

• Classifies viruses based on their nucleic acid type (DNA or RNA).
• Categorizes viruses by single-stranded (ss) or double-stranded (ds) nucleic acid.
• Considers the viral replication method.
• Classes:
  • Class 1: dsDNA viruses (e.g., Adenoviruses, Herpesviruses, Poxviruses)
  • Class 2: ssDNA viruses (e.g., Parvoviruses)
  • Class 3: dsRNA viruses (e.g., Reoviruses)
  • Class 4: ssRNA viruses (positive sense) (e.g., Picornaviruses, Togaviruses)
  • Class 5: ssRNA viruses (negative sense) (e.g., Orthomyxoviruses, Rhabdoviruses)
  • Class 6 & 7: Reverse transcriptase viruses (ssRNA or dsRNA, RNA used as a template for DNA synthesis) (e.g., Retroviruses, Hepadnaviruses)

Nucleic Acids in Cells and Viruses

• Cells have dsDNA with a double helix structure.
• Messenger RNA (mRNA) in cells is single-stranded.
• Viruses can have:
  • dsRNA (resembles dsDNA)
  • ssRNA (positive or negative sense)
• Viruses have a small number of genes, which express a small number of proteins.
• When a virus enters a host cell, its nucleic acid often needs to be converted into mRNA for protein synthesis by the host cell's ribosomes.
• Exception: Positive-sense ssRNA viruses can be directly read by ribosomes.

Class 1 Viruses: Double-Stranded DNA (dsDNA)

• Clinically significant examples: herpesviruses and papillomaviruses
  • Herpesviruses: e.g., Herpes Simplex Virus (HSV), Varicella-Zoster Virus (VZV), Cytomegalovirus (CMV)
  • Papillomaviruses: Human Papillomavirus (HPV)
• Replication and transcription in host cells:
  • Similar to the process in mammalian cells with dsDNA.

Class 2 Viruses: Single-Stranded DNA (ssDNA)

• Carry one molecule of DNA.
• Clinically significant example: parvoviruses
  • Parvoviruses: e.g., Parvovirus B19
• Replication and transcription:
  • Requires conversion to dsDNA before the host cell can process it.

Class 3 Viruses: Double-Stranded RNA (dsRNA)

• Clinically significant example: rotaviruses (common cause of viral diarrhea)
• dsRNA:
  • Unusual in cells, triggers a strong immune response.
  • Recognized by toll-like receptors.
• Viruses must evade the immune response.

Class 4 and 5 Viruses: Single-Stranded RNA (ssRNA)

• Positive Sense (Class 4):
  • RNA is in the same direction as mRNA.
  • Can be directly read by ribosomes for protein synthesis.
  • Examples: SARS-CoV-2 (COVID-19), other SARS viruses, MERS viruses, poliovirus, rhinovirus, dengue fever, hepatitis C, rubella.
  • Picornaviruses: e.g., Poliovirus, Rhinovirus
  • Togaviruses: e.g., Rubella virus
• Negative Sense (Class 5):
  • RNA is a mirror image of mRNA.
  • Requires a copy to be made into the correct orientation for ribosomes to read.
  • Viruses carry a protein for copying RNA, which makes mistakes, aiding immune evasion.
  • Examples: influenza virus, rabies, measles, mumps.
  • Orthomyxoviruses: e.g., Influenza virus
  • Rhabdoviruses: e.g., Rabies virus

Class 6 and 7 Viruses: Reverse Transcriptase RNA Viruses

• Use reverse transcription: RNA is used as a template to make DNA.
• Viruses bring an enzyme to read RNA and make DNA.
• Clinically important example: HIV (human immunodeficiency virus)
  • Can be targeted with therapies.

Viral Replication Process (Five Steps)

• Attachment: Virus attaches to the host cell.
  • Proteins on the virion surface attach to complementary molecules on host cells (e.g., glycoproteins, glycolipids, receptors).
  • $SARS CoV 2$ (COVID-19) attaches to $ACE2$ receptors.
• Penetration and Uncoating: Virus enters the host cell and releases its nucleic acid.
  • The whole capsid enters, and uncoating happens inside the cell.
  • Penetration and uncoating can occur in a single step, like injecting DNA into the host cell.
  • Phages leave the protein coat outside the cell, and only genetic material enters.
  • Enveloped viruses fuse with the plasma membrane to release the capsid.
  • Viruses can enter via endocytosis or phagocytosis.
• Transcription and Translation: Viral genetic material is read and converted into proteins.
  • Viruses carry a small number of genes.
  • Virus proteins are divided into early and late phase proteins.
  • Capsids are made up of capsomeres (virus only needs to encode one type of protein).
  • DNA viruses use DNA-dependent RNA polymerase to make mRNA.
  • DNA-dependent: enzyme reads DNA code and makes a complementary copy of RNA.
  • Double-stranded RNA viruses need an RNA-dependent RNA polymerase.
  • molecule that can read the RNA and make RNA out of that.
  • Positive-sense ssRNA viruses can be directly read as mRNA.
  • Negative-sense ssRNA viruses need to carry an RNA-dependent RNA polymerase to make mRNA.
  • Translation: ribosomes read mRNA and assemble amino acids into proteins.
• Genome Replication: Virus genome is copied.
• Assembly, Maturation, and Release: New virus particles are assembled and released.
  • Small viruses (e.g., tobacco mosaic virus, polioviruses) self-assemble.
  • Most viruses are released by cell lysis.
  • Enveloped viruses bud off from a membrane area.

Intracellular Processes in Viral Replication

• Viruses enter host cells using membrane proteins that facilitate attachment.
  • Examples: sialic acid-rich glycoproteins, proteoglycans, receptors (LDL, CD4), proteins forming tight junctions (oculins, cloudins).
• Enveloped virions fuse with the plasma membrane.
• Non-enveloped virions are endocytosed.
• Virions are transported along cytoskeletal filaments.
• RNA viruses' genomes enter the cytoplasm through uncoating, triggered by endosomal pH.
• Viral RNA transforms into mRNA for protein translation.
• Viral mRNA can encode multiple proteins through mRNA folding patterns (IRES) or splitting the translated peptide chain.
• Early proteins are involved in replication processes and made in smaller amounts.
• Late (structural) proteins form new capsids and are produced in large quantities.
• Virions release through exocytosis, budding, or cell lysis.
  • Exocytosis: viral particles travel through the endoplasmic reticulum and Golgi apparatus; undergo pH-dependent maturation.
  • Budding: viral proteins incorporate into the host membrane; viral components assemble at the budding site.
  • Cell Lysis: viruses disrupt the plasma membrane, killing the host cell.

DNA Virus Replication

• Genome delivered to the host nucleus for transcription.
• Uncoating followed by the nuclear import of the DNA.
• Viral DNA transformed into positive-sense dsDNA for transcription.
• mRNA travels to the cytoplasm for translation.
• DNA replication occurs in the cell's nucleus.
• Viral structural proteins are transported to the nucleus for self-assembly.
• Virions penetrate the nuclear membrane by vesicle formation and are released from the cell.

General Virus Information

• Viruses are everywhere; we ingest, inhale, and take in millions every second.
• Viruses infect pretty much all life on Earth, including bacteria and other viruses.
• Viruses are tiny and not visibly seen.
• Most scientists consider viruses as non-living, complex organic matter that self-replicates.
• Viruses consist of a protein shell with DNA or RNA and replication enzymes inside.

Virus Composition and Function

• Virus = strand of genetic information (DNA or RNA, single or double-stranded).
• Uses molecular machines to replicate but needs a host cell.
• Cells manufacture proteins, replicate DNA, and store resources.
• Viruses infect cells and convert them into virus-producing entities.
• The outer protein coat has receptors to bind to a specific cell membrane.
• After joining, the virus uses pathways to force the cell to accept genetic material or take in the virus.
• Virus hijacks protein manufacturing and DNA replication mechanisms.
• After integration, the cell replicates viral DNA and manufactures viral proteins, creating copies of the virus.
• Viruses burst from the cell and infect new hosts.

Outcomes of Viral Infections

• Phage Infections
  • Lytic Cycle: Virus replicates and lyses the host cell, releasing new phages.
  • Lysogenic Cycle: Viral genetic material integrates into the host cell's genome, becoming a prophage. The bacterium is modified, replicates more rapidly, and copies the viral DNA. Sometimes, it reverts to the lytic cycle.

Human Infections

• Acute Infections: Rapid development, severe symptoms, and quick recovery (e.g., common cold, mumps, influenza).
• Persistent Infections: Occur over a longer period (latent, chronic, or slow infections).
  • Latent Infections: Acute episodes with periods where the virus is not detected (e.g., herpes simplex virus, herpes varicella-zoster virus).
  • Virus hides in the nerve ganglion.
  • Chronic Infections: Viral load is always present, causing some illness (e.g., hepatitis B infection).
  • Affects the hepatic cells of your liver.
  • Slow Infections: Long incubation period and slow progression (e.g., HIV).
  • The virus will remain in your body, but it then is very slowly incubating in your body, and that happens over a number of years.
  • They might get a number of years where they're not showing any signs or symptoms of the disease, And then gradually, it's a bit of a tussle between your immune system and the virus.
  • Virus specifically infects t cells of your your immune system.
  • When the $t$ cell count drops below a certain level and the viral load increases at that point, we refer to that as AIDS
  • Immunocompromised they can't fight off.
• Cell Transformation: Viruses transform cells into tumor cells (oncoviruses).
  • Methods: producing a new oncogene in the host cell or altering the expression of host proto-onc