Describe the general properties, structure and classification of viruses. Describe the steps of viral replication.

Definition and General Properties

Structure

• The complete infectious particle is the virion
• Nucleic acid (the genome) — DNA or RNA, single- or double-stranded, linear or circular, segmented or unsegmented
• Capsid — the protein coat, built of repeating subunits called capsomeres. It protects the genome, provides the attachment sites, and carries the main antigens. Nucleic acid + capsid = the nucleocapsid
• Envelope (in some viruses) — a lipid bilayer derived from the host cell membrane during budding, studded with virus-coded glycoprotein peplomers or SPIKES
• Symmetry — icosahedral (cubical), with 20 triangular faces; helical, with capsomeres arranged in a spiral around the nucleic acid; or complex, as in the poxviruses and bacteriophages
• Some viruses carry enzymes within the virion where the host cannot supply them — reverse transcriptase in retroviruses and hepatitis B, and RNA polymerase in negative-sense RNA viruses

Classification

• Classified by the type of nucleic acid, symmetry, presence of an envelope, size, and site of replication
• The baltimore classification groups viruses I to VII by how they generate messenger RNA, which is the step every virus must accomplish
• Three rules for the DNA viruses, each with one exception worth remembering — all are double-stranded except parvovirus (single-stranded); all replicate in the nucleus except poxvirus (cytoplasm, since it carries its own polymerase); and all have icosahedral symmetry except poxvirus (complex)
• Most RNA viruses are single-stranded (except reovirus and rotavirus) and replicate in the cytoplasm (except influenza and retroviruses)

Viral Replication

Adsorption (attachment) — a virion protein binds a specific receptor on the cell surface, which determines the host range and tissue tropism — CD4 and CCR5 for HIV, sialic acid for influenza → penetration — by receptor-mediated endocytosis, or by fusion of the envelope with the cell membrane → uncoating — the capsid is removed and the genome released. From this moment no complete infectious virus can be recovered from the cell — the eclipse phase → biosynthesis — early proteins (enzymes and regulators) are made first, the genome is replicated, then late proteins (structural capsid proteins) → assembly (maturation) — genome and capsid proteins are packaged into new virions → release — by lysis (naked viruses) or by budding through the membrane, acquiring the envelope (enveloped viruses) → The whole cycle takes hours and yields hundreds to thousands of progeny per cell — the one-step growth curve

• The eclipse phase is the fundamental difference from bacterial multiplication — the virus temporarily ceases to exist as a particle and is present only as its disassembled components, which is why viruses cannot be said to divide

Outcomes of Viral Infection at the Cellular Level

Applied Aspects

• Antibiotics have no effect on viruses, because viruses have no cell wall, no ribosomes and no metabolism of their own; prescribing them for viral illness is the single largest source of antibiotic waste and resistance
• Antiviral drugs are few and narrow precisely because the virus uses host machinery, so there are very few targets that are not also host targets; the successful ones exploit virus-specific enzymes such as polymerases and proteases
• Receptor specificity explains tropism and therefore the clinical picture — poliovirus for anterior horn cells, rabies for neurons, HIV for CD4 lymphocytes
• Alcohol hand rub works well against enveloped viruses but poorly against naked ones, which is why hypochlorite is used for norovirus and rotavirus outbreaks and why soap and water remains important
• Vaccination is the principal weapon against viral disease, since treatment options are limited; smallpox has been eradicated and polio nearly so
• Antigenic change is what defeats immunity — the segmented genome of influenza permits reassortment and pandemic shift, and the error-prone reverse transcriptase of HIV generates constant variation
• Latency is why herpesvirus infection is lifelong, and why immunosuppression of any cause reactivates a virus acquired decades earlier