Viruses, Viroids, and Prions: Structure, Replication, and Pathogenicity

Chapter 13: Viruses, Cancer, and Prions

Introduction to Viruses

Viruses are minuscule, acellular infectious agents that carry genetic material in the form of DNA or RNA. Unlike cells, viruses are obligate intracellular parasites, meaning they require a host cell to replicate and cannot carry out metabolic processes independently.

• Acellular: Viruses lack cellular structure and do not possess cytoplasmic membranes, cytosol, or organelles.

• Obligate Intracellular Parasites: They must infect a host cell to reproduce, utilizing the host's metabolic machinery.

• Genome: Viral genomes may be DNA or RNA, single- or double-stranded, linear, circular, or segmented.

• Size: Viruses are typically much smaller than cells, ranging from 10 nm to over 500 nm.

Comparing Cells and Viruses

Cells and viruses differ fundamentally in structure and function. The table below summarizes key differences:

Feature	Cells	Viruses
Cellular Structure	Yes	No
Metabolism	Present	Absent
Growth	Present	Absent
Reproduction	Self-replicating	Dependent on host
Genetic Material	DNA and RNA	DNA or RNA (never both)
Size	200 nm – 12 cm	10 nm – 500 nm

Structure of Viruses

Viruses exist in two states: extracellular (virion) and intracellular. The virion consists of a nucleic acid core surrounded by a protein coat (capsid), and in some cases, an envelope derived from the host cell membrane.

• Capsid: Protein shell that protects the viral genome and aids in attachment to host cells.

• Envelope: Present in some animal viruses, composed of a phospholipid bilayer and viral proteins (often glycoprotein spikes).

• Enzymes: Some viruses carry enzymes necessary for their replication cycle.

Viral Morphologies

Viruses display a variety of shapes, including helical, polyhedral, and complex forms. Bacteriophages, viruses that infect bacteria, often have a complex structure with a head, tail, and tail fibers.

Relative Sizes of Viruses

Viruses are much smaller than most cells and organelles. The following image compares the sizes of various viruses, bacteria, and eukaryotic cells.

Viral Envelopes

Some animal viruses possess an envelope acquired from the host cell during replication. The envelope contains viral glycoproteins that facilitate host cell recognition and entry. Enveloped viruses are generally more sensitive to environmental conditions than nonenveloped viruses.

Host Range and Specificity

Viruses exhibit specificity for their host due to interactions between viral surface proteins and host cell receptors. Most viruses infect only specific cell types or species, though some are generalists.

Genetic Material of Viruses

Viral genomes are highly diverse and are a primary means of classification. They may be:

• DNA or RNA (never both)

• Single-stranded (ss) or double-stranded (ds)

• Linear, circular, or segmented

• Positive-sense (+) or negative-sense (−) RNA

Classification of Viruses

Viruses are classified based on:

• Type of nucleic acid (DNA or RNA, ss or ds)

• Host range

• Size and shape

• Capsid structure

• Presence or absence of an envelope

Viral Replication

Lytic Replication Cycle

The lytic cycle is a replication process resulting in the destruction of the host cell. It consists of five steps:

1. Attachment: Virus binds to host cell surface.

2. Entry: Viral genome enters the host cell.

3. Synthesis: Host machinery synthesizes viral components.

4. Assembly: New virions are assembled.

5. Release: Host cell lyses, releasing new virions.

Lysogenic and Latent Replication

Some viruses can integrate their genome into the host's DNA, entering a dormant state (lysogeny in bacteriophages, latency in animal viruses). The viral genome, called a prophage or provirus, can reactivate later to enter the lytic cycle.

Replication of Animal Viruses

Animal viruses may enter host cells by direct penetration, membrane fusion, or phagocytosis. The replication strategy depends on the type of viral genome (DNA or RNA, ss or ds).

• DNA viruses: Often replicate in the nucleus.

• RNA viruses: Usually replicate in the cytoplasm.

• Retroviruses: Use reverse transcriptase to synthesize DNA from RNA.

Assembly and Release of Animal Viruses

Most DNA viruses assemble in the nucleus, while RNA viruses assemble in the cytoplasm. Enveloped viruses are released by budding, causing persistent infections, while nonenveloped viruses are released by lysis or exocytosis.

Latent Replication of Animal Viruses

Latent viruses (proviruses) can remain dormant within host cells, sometimes for years, evading the immune system. If integrated into host DNA, the provirus becomes a permanent part of the host genome.

Bacteriophage vs. Animal Virus Replication

Step	Bacteriophage	Animal Virus
Attachment	Proteins on tails attach to cell wall	Spikes, capsids, or envelope proteins attach to cell membrane
Penetration	Genome injected or diffuses into cell	Capsid enters by penetration, fusion, or endocytosis
Uncoating	None	Capsid removed by enzymes
Site of Synthesis	Cytoplasm	RNA viruses: cytoplasm; DNA viruses: nucleus
Release	Lysis	Exocytosis, lysis, or budding
Chronic Infection	Lysogeny	Latency

Examples of Viruses

Human Immunodeficiency Virus (HIV)

HIV is a retrovirus with a double-stranded RNA genome. It carries reverse transcriptase, integrase, and protease enzymes, infecting CD4 T-cells and macrophages. The replication cycle involves attachment, entry, reverse transcription, integration, synthesis, assembly, and release.

Influenza Virus

Influenza is an RNA virus with a segmented genome and envelope glycoproteins hemagglutinin (H) and neuraminidase (N). Antigenic drift (minor changes) and shift (major changes) in these proteins can lead to new strains and pandemics.

Viruses and Cancer

Oncogenic Viruses

Some viruses can cause cancer by disrupting normal cell cycle regulation. Mechanisms include insertional mutagenesis (disrupting tumor suppressor genes), upregulation of oncogenes, or carrying viral oncogenes.

• Examples: Epstein-Barr virus, Human papillomavirus (HPV), Hepatitis B and C viruses, HIV, Human herpesvirus 8, HTLV-1.

Other Parasitic Particles: Viroids and Prions

Viroids

Viroids are small, circular, single-stranded RNA molecules that infect plants. They lack a protein coat and do not code for proteins, causing disease by interfering with plant RNA.

Prions

Prions are infectious proteins that cause neurodegenerative diseases. The normal cellular form (PrPC) has α-helices, while the disease-causing form (PrPSc) has β-pleated sheets. Prions propagate by inducing misfolding of normal proteins.

• Diseases: Bovine spongiform encephalopathy (BSE), Scrapie, Chronic wasting disease, Kuru, Creutzfeldt-Jakob disease (CJD).

• Treatment: Prions are resistant to standard sterilization; only incineration is effective.

Comparison Table: Bacteria, Viruses, Viroids, Prions

Feature	Bacteria	Viruses	Viroids	Prions
Width	200–2000 nm	10–400 nm	2 nm	5 nm
Length	200–550,000 nm	20–800 nm	40–130 nm	5 nm
Nucleic Acid	DNA and RNA	DNA or RNA	RNA only	None
Protein	Present	Present	Absent	Present (PrP)
Cellular	Yes	No	No	No
Cytoplasmic Membrane	Present	Absent (some have envelope)	Absent	Absent
Functional Ribosomes	Present	Absent	Absent	Absent
Growth	Present	Absent	Absent	Absent
Self-Replicating	Yes	No	No	No; transforms PrP protein
Responsiveness	Present	Some bacteriophages respond	Absent	Absent
Metabolism	Present	Absent	Absent	Absent

Families of Human Viruses

DNA Viruses

Family	Strand Type	Representative Genera (Diseases)
Poxviridae	Double	Orthopoxvirus (smallpox)
Herpesviridae	Double	Simplexvirus (herpes), Varicellovirus (chickenpox), Epstein-Barr virus (mononucleosis, Burkitt’s lymphoma)
Papillomaviridae	Double	Papillomavirus (warts, cervical cancer)
Polyomaviridae	Double	Polyomavirus (leukoencephalopathy)
Adenoviridae	Double	Mastadenovirus (conjunctivitis, respiratory infections)
Hepadnaviridae	Partial single/double	Orthohepadnavirus (hepatitis B)
Parvoviridae	Single	Erythrovirus (erythema infectiosum)

RNA Viruses

Family	Strand Type	Representative Genera (Diseases)
Picornaviridae	Single, +	Enterovirus (polio), Hepatovirus (hepatitis A)
Caliciviridae	Single, +	Norovirus (gastroenteritis)
Astroviridae	Single, +	Astrovirus (gastroenteritis)
Hepeviridae	Single, +	Hepevirus (hepatitis E)
Togaviridae	Single, +	Alphavirus (encephalitis), Rubivirus (rubella)
Flaviviridae	Single, +	Flavivirus (yellow fever), Hepacivirus (hepatitis C)
Coronaviridae	Single, +	Coronavirus (common cold, SARS)
Retroviridae	Single, +, segmented	Deltaretrovirus (leukemia), Lentivirus (AIDS)
Paramyxoviridae	Single, −	Paramyxovirus (common cold), Morbillivirus (measles)
Rhabdoviridae	Single, −	Lyssavirus (rabies)
Filoviridae	Single, −	Filovirus (Ebola), Marburgvirus
Bunyaviridae	Single, −, segmented	Bunyavirus, Hantavirus
Orthomyxoviridae	Single, −, segmented	Influenzavirus (flu)
Arenaviridae	Single, −, segmented	Lassavirus
Reoviridae	Double, segmented	Orbivirus, Rotavirus