Intro to Viruses: Classification & Characteristics

Okay, here are your updated study notes, incorporating the new information provided:

Viruses

• First identified as "filterable agents" due to their small size
• Defined as obligate intracellular parasites, as they depend on the host's biochemical machinery for replication
• Reproduce through the assembly of individual components rather than binary fission, assembling macromolecules
• Consist of nucleic acid, protein, and sometimes a membrane envelope (enveloped or naked)
• The physical structure and genetics are optimized through mutation and selection for infecting hosts
• Classifications are based on viral characteristics, the diseases they cause, or their geographic origin

Classification methods for viruses

• By viral characteristics (e.g., picornavirus)
• By the diseases they cause (e.g., poxviruses)
• By the tissue or geographic location where they were first identified (e.g., Norwalk virus)
• By physiological and biochemical characteristics:
  • Size (some may be as big as bacteria)
  • Morphology (presence or absence of an envelope)
  • Type of genome
  • Means of replication

Families of DNA viruses

• DNA viruses associated with human disease fall into 7 families
• Poxviridae: includes smallpox, vaccinia, monkeypox, canarypox, and molluscum contagiosum viruses
• Herpesviridae: includes herpes simplex virus types 1 and 2, varicella-zoster virus, Epstein-Barr virus, cytomegalovirus, and human herpesviruses 6, 7, and 8
• Adenoviridae: includes adenovirus
• Hepadnaviridae: includes hepatitis B virus
• Papillomaviridae: includes papilloma virus
• Polyomaviridae: includes JC virus, BK virus, and SV40
• Parvoviridae: includes parvovirus B19 and adeno-associated virus

Families of RNA viruses

• RNA viruses are divided into at least 13 families
• Paramyxoviridae: e.g., parainfluenza virus, Sendai virus, measles virus, mumps virus, respiratory syncytial virus and metapneumovirus
• Orthomyxoviridae: includes influenza virus types A, B, and C
• Coronaviridae: includes coronavirus and severe acute respiratory syndrome
• Arenaviridae: includes Lassa fever virus and lymphocytic choriomeningitis virus
• Rhabdoviridae: includes rabies virus and vesicular stomatitis virus
• Filoviridae: e.g., Ebola virus and Marburg virus
• Bunyaviridae: e.g., California encephalitis virus, La Crosse virus, sandfly fever virus, hemorrhagic fever virus, and Hanta virus
• Retroviridae: includes human T-cell leukemia virus types I and II, human immunodeficiency virus
• Reoviridae: e.g., rotavirus and Colorado tick fever virus
• Togaviridae: e.g., rubella virus and Venezuelan equine encephalitis virus
• Flaviviridae: includes yellow fever virus, dengue virus, St. Louis encephalitis virus, West Nile virus, hepatitis C virus, and Zika
• Caliciviridae: e.g., Norwalk virus and calicivirus
• Picornaviridae: e.g., rhinoviruses, poliovirus, echoviruses, coxsackievirus, and hepatitis A virus
• Delta: includes delta agent

Virion Structure

• Virion sizes range from 18 nm (parvoviruses) to 300 nm (poxviruses)
• Larger virions can carry larger genomes, capable of encoding more proteins and making them more complex
• A virion (virus particle) consists of:
  • Nucleic acid genome
  • Capsid (protein coat forming the nucleocapsid)
  • Sometimes an envelope (membrane) and essential/accessory enzymes for replication

Viral Genome

• The genome can be DNA, which can be single-stranded, double-stranded, linear, or circular,
• RNA genomes can be positive-sense (like mRNA), negative-sense, double-stranded, or segmented

Attachment

• Surface structures of the capsid and envelope mediate interactions with the target cell via a viral attachment protein (VAP)
• Disruption of the outer packaging inactivates the virus, and antibodies can prevent infectious disease by targeting it

Capsids

• Capsids provide a rigid structure that is resistant to environmental conditions, acids, and detergents
• Capsid viruses are assembled from protein subunits, protomers, capsomeres, and procapsids
• Components have chemical features that allow assembly into a larger unit

Envelopes

• Membranous structures only maintained in aqueous solutions
• Readily disrupted by drying, acidic conditions, detergents, and solvents
• Must remain wet and are generally transmitted in respiratory droplets, blood, and tissue

Symmetry

• Helical viruses often appear as rods
• Icosahedral viruses are symmetric

Enveloped viruses

• Possess envelopes composed of lipids, proteins, and glycoproteins, derived from cellular membranes
• Cellular proteins are typically not found in the viral envelope
• Most show round or pleomorphic shapes, except for exceptions like poxviruses and rhabdoviruses

Viral Replication

• Involves virus recognition, attachment to an appropriate target cell, penetration of the plasma membrane, and uncoating of the genome
• Starts with genome replication and viral macromolecular synthesis
• Proceeds through viral assembly and release
• Enveloped viruses enter by endocytosis or membrane fusion, with the capsid injecting into the cell
• The cell as a factory provides substrates, energy, and machinery necessary for viral protein synthesis and genome replication
• Some processes are not provided by the host cell, so they must be encoded in the genome of the virus

Early Phase and Late Phase

• Early phase ends with uncoating its genome
• Late phase begins with genome replication

Uncoating

• Abolishes infectivity and renders its identifiable structure
• Eclipse period is when there is no identifiable structure of the virus and ends when new virions appear
• Extracellular infectious virus is not detected
• Latent includes the eclipse period and ends with the release of new viruses
• Burst size refers to the yield of infectious virus per cell

DNA Viruses- Key Facts

• Replication requires a DNA-dependent DNA polymerase, other enzymes, and dNTPs
• The viruses use host cell polymerases and other enzymes for viral mRNA synthesis during transcription
• Promote their own viral genes during transcription

DNA Viruses replication

• Initiation occurs at a unique DNA sequence named the origin (ori)
• Viruses use cellular or viral nuclear factors and DNA-dependent DNA polymerase from the host or viral origin
• Is semiconservative
• Viral polymerases are usually faster but less precise

Replication Limits of DNA Viruses

• Replication is subject to limits:
  • availability of DNA polymerase and dNTPs
  • Most cells in a resting phase of growth are not undergoing DNA synthesis, necessary enzymes are not present and dNTP pools are limited
  • The smaller the virus more dependent it is on the host cell

Types of Viral Transcripts

• Immediate Early: proteins that regulate
• Early: structural proteins/ genome replication
• Late; 3 structural virion proteins

RNA Polymerases

• Don't require RNA primer
• Cellular primase (RNA primer)

Viral Replication Target

• Viral enzymes are often targeted for drug interventions

Enveloped Viruses

• Naked: Lysis + release, kills host.
• S'enveloped: budding + release, does not kill host cell

Retroviruses like HIV

• Integrate Viral DNA Into Host Cell Chromosome
• Target Helper T cells, and use CD4 receptor and cytokine Coreceptor
• Carries enzymes with it into host cell

Positive Sense Strands in Cytoplasm

• In retroviruses cDNA is synthesized in the cytoplasm, travels to the nucleus, and then the viral DNA integrates into the host genome

Viral protein

• The surface envelope proteins (gp120/41) are translated in the rough ER, modified in the golgi then expressed in the cell membrane
• This allows for new viruses to bud off without lysing the host cell
• 2 (+) mRNAs are packaged into new virions

Neuraminidase (NA)

• Allows it prevent clumping and facilitate release

Re-initiation of Replication

• Can occur:
  • Via cell-to-cell bridges (herpes)
  • Occurs through cell-to-cell Fusion
  • Vertically to daughter cells (RSV)

Replication Details

• RNA Viruses work at a fast pace but cause mutations
• Positive-strand RNA viral genomes, naked + strand RNA, are sufficient to initiate an infection itself
• For negative-strand RNA viral genomes, the - strand RNA viral genome is not infectious by itself, and must carry the polymerase into the cell with its genome

Viral Replication Type 1

• interferons interfering with viral replication
• part of endogenous attack against viral infections - Jac/stat cascade - Interferon stimulated - Examples = PKR protein kinase R / GAS oligo A synthase (RNASCI)/ MxgTPase All additions from the new text are italicized. I hope this helps!