622 10/28 GLA pt 3 Bacteria and Viruses

Obligate Intracellular Parasites

viruses depend on host for replication and survival

Viruses

10-100x smaller than host cell, cannot be seen using light microscope, must be visualized using electron microscope

has to use host resources, disrupting host homeostasis and contributing to clinical presentation

Bacteria vs Virus Chart

Acellular

distinguishes viruses, no ribosomes for protein synthesis, no mito for energy, no metabolic enzymes for biochemical processes, can’t make ATP

Receptors

specific cellular structures that viruses need to identify adn bind to, determines tissue tropism and species specificity

3 Components of Viral Structure

genetic material (either DNA or RNA)

capsid (protective protein shell)

outer lipid envelope (not always)

Virion

virus particle, complete infectious virus, extracellular, outside of host cells

nucleic acid genome surrounded by protein coat and sometimes additional layers of material (envelope)

What facilitates transmission of a virus between host cells?

virion

Virion Diagram

Ligand

on virus particle to help it bind to host, often part of capsid shell or the envelope

interact with receptors on host

Ligands and Receptors

ligand of virus particle matches host receptor like a key and lock

determines virus’s tropism and host range

DNA Viruses

most posess dsDNA (double-stranded), linear or circular, range from small as 5kb to large as 200 kb

icosahedral capsid, replicate in nucleus, use host enzymes for replication

ssDNA

only present in parvoviridae family

RNA Viruses

posess +ssRNA (single-stranded positive-sense), -ssRNA (single-strand negative-sense), and dsRNA

Segmented Genome

quality of some RNA viruses (influenza and rotavirus) that enable genetic reassortment and greater evolutionary flexibility

RNA Virus Mutation Rate

10,000x higher than DNA viruses bc of lack of proofreading mechanism in RdRp

contributes to rapid viral evolution, antigenic drift, and challenges in vaccine development and long-term immunity

RNA-dependend RNA polymerases (RdRp)

enzyme that RNA viruses use to copy their genome, no proofreading mechanism

Capsid

protective protein shell, surrounds and protects viral genome while facilitating attachment and entry into host cells

Isocaheral Capsids

most common, 20 triangular faces arranged in a symmetrical structure

provides maximum internal volume with minimal protein requirements, making it highly efficient for viral replication

Adenoviruses

have icosahedral capsid, cause respiratory infections and HPV (leads to cervical cancer)

Helical Capsids

form cylindrical structures where capsid proteins spiral around the viral RNA genome

all medically important ones are enveloped (influenza and measles)

Complex Capsids

combine icosahedral and helical to make elaborate structures

Poxviridae Family

DNA virus, differ from other DNA viruses in that they have a complex capsid and replicate in the cytoplasm, includes smallpox and molluscum contagiosum

brick-shaped or ovoid capsids with complex internal structures that accomodate their large DNA genomes and numerous viral enzymesaccommodate

What do viral envelopes impact?

viral stability, transmission routes, and clinical management strategies

Enveloped Viruses

acquire a lipid bilayer membrane derived from host cell membranes during the budding process

more fragile and susceptible to environmental factors such as heat, detergents, and desiccation

Naked (Non-Enveloped) Viruses

only the genome and capsid

environmentally stable and can survive on surfaces, in water, and under harsh conditions for extended periods

Naked (Non-Enveloped) Viruses Examples

norovirus gastroenteritis, adenoviral conjuctivitis

Naked (Non-Enveloped) Viruses Spread

fecal-oral transmission, environmental spread

Enveloped Viruses Spread

direct contact with bodily fluids, respiratory droplets, blood, or organ transplantation

Enveloped Viruses Examples

HIV, hepatitis B, herpesviruses

Glycoproteins

in viral envelope, attachment proteins that determine host cell specificity and serving as important targets for neutralizing antibodies and antiviral drugs

Virus Infection of Host Cell Stages

attachment/absorption of virus to a susceptible host cell

entry/penetration of the virion or its nucleic acid

synthesis of virus nucleic acid and protein by cell metabolism as redirected by virus

assemble of capsids and packaging of viral genomes into new virions (maturation)

release of mature virions form the host cell

Virus Infection of Host Cell Stages Diagram

Attachement Inhibitors

block initial virus-cell interactions by targeting viral attachment proteins or cellular receptors

Entry Inhibitors

target the membrane fusion processes

Uncoating Inhibitors

prevent viral genome release

Replication Inhibitors

largest class of antiviral drugs, target viral polymerases

Assembly and Release Inhibitors

offer newer therapeutic approaches including protease inhibitors that prevent proper viral protein processing and release

Combination Therapy

target multiple life cycle stages simultaneously, reducing the likelihood of resistance development

Abortive Infections

when virus enters cell but doesn’t complete replication cycle due to cellular restrictions or inadequate viral factors

may produce defective viral particles or incomplete viral proteins but do not generate infectious progeny

Abortive Infections Clinical Presentation

minimal symptoms, sometimes trigger immune responses and contribute to chronic inflammation in some cases

Acute Viral Infections

most recognizable, virus replicates with significant cytopathic effects, leading to cell death and tissue damage

Acute Viral Infections Clinical Presentation

rapid onset, intense symptoms, relatively short duration

predictable pattern of incubation, prodromal symptoms, peak illness, and resolution as the immune system clears the infection

Acute Viral Infections Examples

rhinovirus common colds, influenza infections, gastroenteritis caused by norovirus

Subacute Sclerosing Panencephalitis (SSPE)

delayed complication fo acute infection following measles

shows that even apparently resolved acute infections may have long-term consequences

Latency Viral Infections

long-term persistence, dormancy and reactivation

during latency, they produce minimal or no viral proteins so it can avoid host immune response

Herpes Simplex Virus (HSV)

establishes latency in sensory ganglia and reactivating during periods of immunosuppression or stress

Clinical Significance of Latent Infections

associated with malignant transformations (EBV, HPV, HHV-8 → cervical carcinoma, burkitt lymphoma, kaposi sarcoma)

Chronic Viral Infections

persistent viral replication and shedding over extended periods (years to decades)

Inclusion Bodies

most diagnostically useful cytopathic effect, distinct intracellular structures containing viral components

Nuclear Inclusion Bodies

relfect sites of viral replication and assembly

ex: pathognomonic “owls eye” inclusion in CMV and cowdry type a inclusions in HSV

Cytoplasmic Inclusion Bodies

often contain viral nucleocapsids, replication complexes, or viral proteins and can be identified through routine histopathology or immunofluorescence techniques

ex: negri bodies in rabies, acidophilic inclusions in poxyvirus

Syncytia Formation

can facilitate spread between cells while potentially helping viruses evade immune recognition by avoiding extracellular response

cytopathic effect where infected cells fuse to create multinucleated giant cells, caused by viral fusion proteins (HSV, VZV, paramyxoviruses, HIV)

Slow Viral Infection

prolonged incubation periods followed by gradual onset of neurological symptoms

ex: JC virus leads to PML

What does the type of genetic material of a virus determine?

where the replication occurs within the host cell, which enzymes are required, and what therapeutic targets are available

Baltimore Classification

organizes viruses into 7 classes based on their genome type and pathway used to make mRNA for protein synthesis

Baltimore Classification Diagram

Class I Viruses

dsDNA, replicative similarity to host cell DNA, uses host cell DNA polymerase and transcription machinery

Class II Viruses

+ssDNA, must first convert genome to dsDNA before transcription

Class III Viruses

dsRNA, carry their own RdRp to transcribe mRNA

Class IV Viruses

+ssRNA, genome serves directly as mRNA, replicates in cytoplasm

Class V Viruses

-ssRNA, carry their own RdRp for transcription

Class VI Viruses

+ssRNA-RT, reverse-transcribing, reverse transcribe their RNA genome into DNA that integrates into the host chromosome

ex: HIV

Class VII Viruses

dsDNA-RT, reverse-transcribing, use reverse transcription as part of their replication cycle but maintain DNA genomes

ex: hepatitis B

Fidelity

most DNA viruses use host cell DNA polymerase with 3’ to 5’ exonuclease proofreading activity, creating genetically stable viruses and selective antiviral targeting more challenging

Quasispecies

viral populations with extensive genetic diversity, results from RNA viruses using RdRps

allows rapid adaptation to selective pressures, including immune responses and antiviral drugs

What does the genetic stability of DNA viruses allow for?

more durable immune responses and more effective vaccination strategies

ex: hep b and HPV vaccines

What do high mutation rates in RNA viruses contribute to?

drug resistance development, necessitating combination therapy approaches

ex: HIV and hep c

Parvoviridae

DNA virus that is ssDNA and naked

RNA Virus Classification

Characteristics of RNA Viruses

contain RNA, replicate in cytoplasm

classified based on morphology of capsid and structure of genetic material

+ssRNA Viruses

contain RNA that can be directly translated by host cell because it is the most similar to the host cell mRNA

use host ribosomes to make proteins that function to replicate the virus

host ribosome synthesizes RdRp from RNA

-ssRNA Viruses

have RNA that is complementary to the translatable mRNA, must be transcribed before it can be used for protein synthesis

carry their own RdRp that transcribes it into a translateable RNA that the host can then translate into a protein and use for viral replication

dsRNA Viruses

carry RdRp, replicate the same as -ssRNA

recognized as foreign to host cell and will activate type i IFNs, so part of the replication cycle takes place in a viral particle

Retroviruses

can reverse transcribe their RNA genome into DNA using reverse transcriptase, allows genetic material from retovirus to become a permanent part of the DNA of an infected cell

ex: HIV (causes AIDS)

DNA Viruses

contain DNA, most are dsDNA and icosahedral (except parvoviridae and poxviridae), replication occurs in nucleus using host enzymes like DNA-dependent RNA polymerase

Exceptions to DNA Virus Replication

herpesviridae and adenoviridae may use their own polymerases for replication rather than the host machinery

RNA Viruses Examples

Key DNA Virus Families and Diseases

Cytopathic Effects

inclusion bodies

syncytia formation

What families of RNA viruses do not replicate in the cytoplasm?

Orthomyxoviridae and Retroviridae families

DNA Viruses Summary