Viruses: Structure, Replication, and Impact

• "Virus" is from the Latin word for "toxin"
• Viruses infect all living things including other viruses
• Viruses affect ecosystems, health, and evolution
• Viroids and prions are virus-like agents that differ in replication
• Viruses are acellular entities needing host cells and their ribosomes
• Within host cells, viruses use the host's metabolic machinery to replicate
• Components self-assemble into infectious particles protecting the genome

Virus v. Living Organisms

• Living organisms have cellular structure, homeostasis, energy production, growth, evolution, responsiveness, and reproduction
• Viruses only evolve, respond to stimuli, and reproduce within a host cell
• Outside a host cell, a virus is non-living and inactive
• Viruses persist in the host population and are genetically programmed to survive and propagate
• Viruses thrive due to rapid progeny generation and high mutation rates, adapting to changing environments
• However, only a small fraction of virus particles infect host cells

Viruses and Global Health

• Viruses significantly impact human health and global mortality differently by region
• All viruses share packaging genetic material for genome transmission and having instructions for new virus particles

Viruses and Genetic Transmission

• Utilise various genome formats but must produce mRNA, as ribosomes only translate mRNA
• Require host ribosomes and must uncoat to release their genetic material
• Act as parasites of the host's protein synthesis machinery

Viruses in the Biosphere

• Outnumbers bacteria by 10 times and co-evolved with life
• They play key roles in evolution, climate regulation, and ecological balance
• Viruses kill about 20% of biomass daily, releasing organic molecules promoting microbial growth
• They primarily recycle carbon in marine environments, with over 10^30 bacteriophages in seawater
• They would stretch 250 million light-years if viral genes were aligned

Human Virome

• Includes eukaryotic viruses and bacteriophages
• Most viruses in virome studies remain unidentified, revealing vast unexplored viral diversity
• Anelloviridae are abundant in immunocompromised individuals but do not cause disease
• Factors shaping the human virome: Diet, breastfeeding, medications, geography, genetics, and aging
• Eukaryotic viruses can cause acute and chronic inflammation and trigger the development of the innate immune system
• Phages interact with the immune system via TLR signaling, modulating bacterial populations and transferring DNA

Endogenous Retroviruses and The Virome

• Approximately 8% of the human genome consists of LTRs
• These come from ancient viral infections, play significant roles in genome structure and evolution
• Negative Virome Impacts
• Chlorovirus, typically found in aquatic environments, was unexpectedly discovered in the human oropharyngeal virome
• Individuals infected with Chlorovirus showed decreased cognitive performance; infected mice exhibited altered gene expression in the hippocampus

The Human Herpes Viruses

• Every person carries at least two of the eight known human herpes viruses:
• Herpes simplex virus type 1 (HSV-1)
• Herpes simplex virus type 2 (HSV-2)
• Varicella-zoster virus (VZV/HHV-3)
• Epstein-Barr virus (EBV/HHV-4)
• Cytomegalovirus (CMV/HHV-5)
• Human herpesvirus type 6 (HHV-6)
• Human herpesvirus type 7 (HHV-7)
• Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8)

The Protective Virome

• Viruses maintain health much like beneficial bacteria
• Murine norovirus (MNV) restored intestinal function in Germ-Free mice compensating for missing gut bacteria
• Enteric viruses replace the beneficial function of commensal bacteria

Viral Entry

• Most viruses interact harmlessly, but entry points are limited to specific sites
• Skin: Strong barrier needing damage
• Mucosal Surfaces: Main entry point of living cells with Mucus, cilia, tight junctions, Enzymes, low pH, antimicrobial peptides, Secretory IgA, dendritic cells, macrophages, interferons

Host/Tissue/Cellular Tropism

• Host: Viruses infect only specific hosts
• Tissue & Cellular : Determined by the presence of receptors and intracellular factors
• Viral Tropism: the ability of a virus to productively infect a host species/tissue/cell
• Factors influencing viral tropism: Receptors on the cell surface, intracellular factors like TF, and the cell's state are required for virus uptake
• Example: Influenza A virus infects humans, mammals, and birds, but receptor patterns restrict infection sites, located deeper in human lungs versus upper bird respiratory tract
• Susceptible cells absorb and enter, permissive cells allow ONLY viral replication

Effects of Viruses on Host Cells

• Structural and biochemical effects on host cells include lysis, exocytosis, budding, and malignant transformation
• HPV and Adenovirus
• HPV: Induces tumour formation
• Adenovirus: Cell dies during lytic infection
• Hepatitis B, Herpes Retroviruses
• Hepatitis B (HBV): Causes persistent infection and slow virus release without cell death
• Herpes Retroviruses: Remain latent and later reactivate

Thermoresistance in Plants/Phage Therapy

• Example of Thermoresistance in Plants: Some help plants survive extreme temperatures
• Example Mucus: Epithelial cells secrete mucus, enhancing replicative success
• Phage Therapy Use: uses bacteriophages to treat targeting drug resistant bacteria

Virus Gene Therapy

• Gene therapy delivers genetic material into cells
• Viruses carry a vector to introduce or modify genes & therapeutic genes without causing disease
• Viral vectors deliver therapeutic genes without causing disease, providing the functional gene as episomal DNA (AAV)
• Integrating into the genome (retrovirus): genetic disorders like SMA and haemophilia and deliver Ags for vector vaccines

Virus Transmission

• Stages: Escape, transport, and entrance into a new host
• Main routes of transmission:
• Airborne: Measles, mumps, coronavirus
• Droplet: Large droplets fall quickly
• Blood-borne: HIV, HBV, HCV and insect-borne (Dengue, yellow fever)
• Food & Water: Polio, Norovirus and Vertical Transmission (HIV, Zika)
• Transmission efficiency depends on stability, replication site, shedding, and host immunity

Transmission Numbers

• Contagiousness is indicated by the basic Reproduction Number (Ro)
• Relates to population immunity and preventative measures & the number of people one sick person will infect on average
• it depends on measures to stop the infection, like masks and vaccines

Virus History

• Viruses lack physical fossils & their age is estimated via genetic changes (molecular clock)
• Evidence indicates they have infected insects for at least 300 million years, possibly influencing the evolution of life from the beginning
• Origin details suffer the lack of fossil evidence, mixing of viral and cellular genes, ability to infect all living organisms and evolve with multiple hosts

Virus Origin

• Hypothesis of Virus Origin
• Virus Early H.: Viruses emerged early in evolution
• Regressive H.: Viruses evolved from once-independent cells that lost translation ability and became parasitic
• Progressive H.: Viruses originated from selfish genetic elements capable of autonomous replication.
• "Virus early" versus Regressive and progressive hypotheses:
• "Virus early" viruses predate cells
• regressive and progressive hypotheses viruses emerged after the first cells formed
• Viruses carry this structure before LUCA diversified into modern cells

Virology Timeline

• Virology started approximately 130 years ago
• earlier evidence of viral infections dates back to human history (Ramses V showed signs of smallpox)
• Early Combatting Efforts
• 1000 BC Blister powder from smallpox sores was inhaled to confer immunity
• 1796 Edward Jenner pioneered vaccination using cowpox to protect against smallpox
• 1885 Louis Pasteur extended vaccination to other diseases
• Virus Discoveries
• 1892 Tobacco mosaic virus (TMV).
• 1898 "filterable agent."
• 1901 human Yellow fever virus significant discoveries followed afterwards in 1903 Rabies virus, in 1906 Variola virus smallpox), in 1908 Chicken leukaemia virus, poliovirus, in 1911 Rous sarcoma virus, in 1915 Bacteriophages, 1933 Influenza virus
• Microscopy and Experiments
• 1935-Tobacco mosaic virus (TMV) was the first virus seen under an electron microscope
• in 1952, Viruses contain genetic material -DNA (not protein) is the genetic material of viruses Hershey-Chase experiment proved Technological Advancements in Virus Discovery: 1890s/1931/1948/1970s/1985/ 2000s and Filtration/Microscopy/PCR sequencing

Discovery of Human Viruses

• Two-thirds of human viruses can infect non-human hosts mammal and bird sources
• Half of these can spread between humans, and some can cause significant outbreaks
• New human viruses will continue to emerge, mainly from mammalian and avian sources
• Metagenomics analyzes genetic material from environmental samples genetic diversity
• Unlike bacteria and archaea, viruses lack a universal genetic marker (e.g 16s or 18S rRNA)
• Revealed 10,000+ species in Antarctica despite low organism diversity

Viral Diversity Estimations

• Wildlife is a significant reservoir for emerging human viruses, like flying foxes model
• Indian Flying Fox (Bat) as Virus Model: Bats harbour many zoonotic viruses but do not get sick due to immune adaptations
• Experiment: Collected throat, faeces, and urine samples. PCR primers in 9 families
• Viruses from 7 families detected. Many viruses previously unknown
• There are 58 viruses in species. If all mammals habitat them, many undiscovered exist

Classification

• Morphology like icosahedral, helical, complex, enveloped, non-enveloped.
• Genome type like RNA, single/double-stranded, segmented, circular
• Replicating mode of organisms : Humans, animals, plants, bacteria and animals zoonotic, lytic, latent, persistent, oncolytic, respiratory, hepatic, neurological.
• Official Virus Taxonomy (ICTV): Since 1970s, the International Committee on Taxonomy of Viruses (ICTV) has regulated classification
• Linnaean: order (-virales)
• • family (-viridae)
• --subfamily (-virinae)
• ---Genus (-virus)
• ----species
• More recent classifications Realm, Kingdom, Phylum, Class, and Order

Genome Types

• Baltimore Group: Divide viruses into seven groups depending on genome/type & mRNA (+/-) Viral Sizes: Range from 20 nm to 300 nm & giant versions challenge traditional virus definitions
• Giant Viruses: Mimivirus was identified in 2003 from 1992 discover, Mimivirus has big range ~911 genes
• Encode not associated (complex like bacteria), lack ribosomal protein
• Suggests a potential fourth domain of life Virophages

Virophages

• Virophages infect viruses - Sputnikvirus. Require co replication parasites.
• May improve host recovery survival by impairing giant virus replication

Part I: Virus Structure (25/02/25)

• diverse structural designs building stable particles & particle/genome structure determines how virus infects a cell, how it replicates/ how it escapes
• summary has limited coding capacity meaning cannot encode large proteins
• viruses follow the principle of genetic economy, using identical copies of one or a few proteins to form the capsid

Symmetry

• Symmetry is essential for capsid formation to self assemble
• Non-covalent interactions hold these structures together

Definitions

• subunit, structural unit, capsid, envelope, nucleocapsid, viral proteins
• Viral Structure Functions & the viral particle has the protect the genome & it forms protective protein
• Delivery ensure successful transfer into host cells
• Stability is maintained and viruses unstable post infection
• The enrcasing is stored in the form of stored energy for genome uncoating of the cell

Types and Symmetry

• Protein subunits helical in center genome- ssRNA
• Flex capped- strength interactions-noncovalets & proteins-bonds
• Animals capsids-wrapped symmetry & animal capsids wrapped

Animal Virus Taxonomy by Family

• Orthomyxoviridae- Influenza (Flu) has Paramyxoviridae (Measles, Mumps), Coronaviridae (SARS), Rabies
• Ebola filovaridae structure Matrix form Capsid- joint forming rigid structures

Capsid Shapes

• Non-identical symmetry
• icosahedron- symmetric shells with internal vol
• Features 5,3 and 2 symmetry

Human Parvovirus

• Human B19 & Cryo-EM & Icosahedras differences T =Structural to unit triangular more faces 6
• Icosahedral number

Icosahedral Configurations

Sedoreoviridae & Rotavirus

• dsRNA viruses
• Segmented Survival
• Double layered for Capsid & GI Tracts
• Glycoslated Spike Proteins Geminivirus (Twinned)
• Plant Viruses
• damage agriculture with unique twined structure one one Vertex
• Single Strand Genome Capsid Structure - Tails

Complex structure

• Tails attached at on vertex - scans, binds, attaches Examples:
• Hexon structural fiber
• penton binds w

Viral Envelope

• Lipid bilayers derived from host cell containing viral glycoproteins forming release budding is crucial for infectivity or entry and are easy to interact and they are derived the cell membrane.

Glycoproteins

• Glycoproteins are integral membrane often oligomeric, are vertically relative to the limit they are involved in attachement

Intracellular Components

• The Intracellular - involves Interactions assembly Proteins Lipo domain - matrix

Non-Structural

• A number of enzymes and Proteases Cellular Components: Histones, tRNAs, lipids, ribosomes.Contains two copies

Virus Tool Development

• Tool like electron microscopy with biological materials and electron scattering
• The X-rays use cryos. To form and density gradients
• The Cryoem- is great for studying crystallis molecules and processes
• Multiple image two dimensional
• Atypical infectuous involop virus

Methods in Virology

• Chamberland Filters & EM
• Physical, cell culture methods & and Immunological tests and genetics
• And virus cultalivation (Animal, embryo-egg cells)

Cell Culture

• Cells are cultured in incubators- grown
• Cell are frozen cyro protect
• Alterations cells/morphologies and cell death caused/ effects cells _CEPs can help identify viruses,

Viral Growth

• Viral growth occurs then uncoat-no life time and is related into infectives
• Quantifies and quantifies by plaque
• Damaged =cant infecr host, can replicate and cell type

Hemagglutination HA

H quantifies the viruses they bind in rbc and infect the virus.

Serological

• is the viral enzymes and M the sequence has to go though analysis and more and the different are analysed

PCR Testing

• Can detect and identify sequence and origin in a specific pattern
• the test can find the new viruses of the clinical environments.

Important human viruses and receptors (04.03.25) Adenoviruses -Non Envelopped

Overview

• non- enveloped linear dsDNA genome w fibers and hexons , cause infections , and occur close settings

Herpesviruses

• large dna, establish

Major Human Herpesviruses: cause viral infections

Flaviviruses

• envelopped, arthopod

Corenoverus

enybolled - animal zoonic

1. Filouiruses - enybolled RNa

End of list