Acellular Pathogens: Viruses, Viroids, and Prions

THE ACELLULAR PATHOGENS

Introduction

Acellular pathogens, including viruses, viroids, and prions, are infectious agents that lack the cellular structure of living organisms. They are significant in microbiology due to their unique biology, mechanisms of infection, and impact on human health.

• Viruses attack all life forms, from bacteria to humans.

• Their existence was first hypothesized by Pasteur.

• Historic viral infections: smallpox, polio.

• Recent viral infections: HIV/AIDS, Ebola, Zika, COVID-19.

CHARACTERISTICS OF VIRUSES

General Properties

• Infectious, acellular, obligate intracellular parasites with host and cell-type specificity.

• Contain either DNA or RNA (never both), surrounded by a protein capsid and, in some cases, a phospholipid envelope with viral glycoproteins.

• Lack genes for many products needed for reproduction; rely on host cell machinery.

• Can infect all types of host cells: plants, animals, fungi, protists, bacteria, and archaea.

• Viruses that infect bacteria are called bacteriophages or simply phages.

HOSTS AND VIRAL TRANSMISSION

• Vectors: Transmission can occur via direct contact, indirect contact (fomites), or animal vectors (e.g., mosquitoes, ticks, flies).

• Disease State: Viruses cause a wide variety of infections; some are highly lethal and difficult to treat.

• Zoonoses: Diseases transmitted from animals to humans (e.g., avian influenza). Reverse zoonoses occur when humans transmit viruses to animals.

VIRAL STRUCTURES

Capsid and Genome

• The capsid is a protein shell composed of subunits called capsomeres.

• The interior contains the viral genome and essential enzymes.

• Virions are much smaller than prokaryotic and eukaryotic cells (20 nm to 900 nm).

Types of Viruses

• Naked (nonenveloped) viruses: Only nucleic acid and capsid.

• Enveloped viruses: Capsid surrounded by a lipid envelope derived from the host cell membrane.

Surface Structures

• Spikes: Protein structures extending from the capsid or envelope, facilitating attachment and entry into host cells (e.g., hemagglutinin and neuraminidase in influenza).

Capsid Shapes

• Helical (e.g., tobacco mosaic virus)

• Polyhedral (e.g., poliovirus, rhinovirus)

• Complex (e.g., bacteriophage, poxvirus)

CLASSIFICATION AND TAXONOMY OF VIRUSES

Formal Classification

• Viruses mutate rapidly, complicating classification by binomial nomenclature.

• The International Committee on Taxonomy of Viruses (ICTV) classifies viruses by genetics, chemistry, morphology, and replication mechanism.

• Family names end in -viridae (e.g., Parvoviridae), genus names in -virus (e.g., Parvovirus).

Informal Groupings

• Naked vs. enveloped

• Single-stranded (ss) or double-stranded (ds) DNA/RNA

• Segmented vs. nonsegmented genomes

• Positive-strand (+) or negative-strand (–) RNA

ICD Codes

• The International Classification of Diseases (ICD) assigns codes to viral infections for clinical tracking (e.g., COVID-19: U07, HIV: B20).

Viral Classification Table (Summary)

Genome & Capsid	Family/Size	Shape	Genus	Associated Infection
ssRNA, naked	Caliciviridae	Icosahedral	Norovirus	Gastroenteritis
ssRNA, envelope	Flaviviridae	Icosahedral	Flavivirus	Yellow fever
dsDNA, naked	Parvoviridae	Icosahedral	Erythrovirus	Fifth disease
dsDNA, envelope	Herpesviridae	Icosahedral	Herpesvirus	Herpes, chickenpox
Additional info: See original slides for more detailed classification.

GENERAL PRINCIPLES OF VIROLOGY

• Viruses are difficult to kill because they reside inside host cells.

• Drugs that kill viruses may also harm host cells.

• Most viral illnesses are self-limiting, but some are severe or fatal.

• Vaccines have prevented many viral diseases; effective antiviral drugs are limited.

VIRAL REPLICATION AND LIFE CYCLES

General Steps

1. Attachment (adsorption)

2. Penetration (entry)

3. Biosynthesis (replication of viral genome and proteins)

4. Assembly (maturation)

5. Release (lysis or budding)

Bacteriophage Life Cycles

• Lytic cycle: Virus replicates and lyses host cell.

• Lysogenic cycle: Viral DNA integrates into host genome as a prophage, replicating with the cell until induced to enter the lytic cycle.

Transduction

• Specialized transduction: Phage transfers bacterial DNA from one cell to another, contributing to genetic diversity.

Animal Virus Replication (e.g., Influenza)

• Similar stages as bacteriophages, but entry may occur via endocytosis or membrane fusion.

• Influenza virus is a notable RNA virus that replicates in the nucleus of host cells.

RNA Virus Biosynthesis

• +ssRNA can be directly translated by host ribosomes.

• –ssRNA must be transcribed to +ssRNA by viral RNA-dependent RNA polymerase (RdRP).

• RdRP and reverse transcriptase are unique to viruses.

HIV: A Special RNA Virus

• HIV is an enveloped retrovirus.

• Uses reverse transcriptase to convert RNA genome to DNA, which integrates into the host genome, causing lifelong infection.

Stages of HIV Infection (WHO Model)

1. Asymptomatic infection

2. Early, general symptoms

3. Moderate symptoms

4. Severe symptoms (AIDS-defining illnesses, often fatal)

VIRUSES AND HUMAN HEALTH

• Viruses are responsible for most human infections, including pandemics (e.g., 1918 H1N1, 2009 H1N1, 2020 SARS-CoV-2).

• Some viruses have high mortality rates (e.g., Ebola).

• Oncoviruses can cause cancer (e.g., HPV, hepatitis B and C).

LABORATORY DIAGNOSIS OF VIRAL INFECTIONS

• Nucleic Acid Amplification Tests (NAAT): Detect viral DNA or RNA in patient samples.

• PCR: Amplifies viral DNA for detection.

• RT-PCR: Converts viral RNA to cDNA, then amplifies it for detection (used for RNA viruses).

PREVENTION AND CONTROL OF VIRAL INFECTIONS

• Immunization (vaccines)

• Education and hygiene (handwashing, safe sex, PPE)

• Antiviral therapies (e.g., highly active antiretroviral therapy for HIV)

VIROIDS AND PRIONS

Viroids

• Small, circular, noncoding ssRNA molecules that infect plants.

• Require a helper virus for replication (e.g., hepatitis delta virus in humans).

Prions

• Infectious proteins that cause neurodegenerative diseases (e.g., Creutzfeldt-Jakob disease, mad cow disease).

• Resistant to heat, chemicals, and radiation; no cure exists.

• Transmission can occur via contaminated food, surgical instruments, or tissue transplants.

TSE in Humans	Mechanism of Transmission
Sporadic CJD	Unknown; possibly somatic mutation
Variant CJD	Eating contaminated cattle products, bloodborne transmission
Familial CJD	Mutation in germline PrP gene
Iatrogenic CJD	Contaminated surgical instruments, tissue transplants
Kuru	Ritualistic cannibalism

Additional info: Prions are unique in that they lack nucleic acids and propagate by inducing misfolding of normal host proteins.