Viral Replication

Phases of cell growth:

1. Lag phase: no increase in number of cells
2. Log phase: exponential increase in number of cells (replication >
death)
3. Stationary phase: number of replicating cells = number of dying cells
4. Declining phase: number of dying cells > number of replicating cells

Cycle growth curve of viruses:

1. Infection: viral load decreases because the virus is entering the cells
leading to lower viremia
2. Eclipse: virus uncoating hence disappears
3. Latent: genetic material has integrated; overlaps eclipse
4. Production/burst: start of the log phase, increased number of cells

Stages of viral replication:

1. Recognition and Attachment: The receptors on the host cell (proteins,
CHO, GP or GL) determine which cells can be infected by a virus:
tropism
Ø Influenza A virus attaches to the sialic acid receptor on epithelial cells through its HA gp
Ø HIV attaches to the CD4 receptor on Th cells via its gp120 protein
2. Penetration: viral entry into the host cell
Ø Enveloped viruses: fuse with the membrane (internal components of the virion are immediatelv delivered to
the cytoplasm of the cell). Herpes viruses, paramyxo viruses, HIV
Ø In HIV: Gp120 binds to CD4 receptor leading to the utilization of a fusion peptide to stabilize the coreceptor.
gp120 undergoes conformational changes after which an ATPase connected to each molecule of gp120 pushes
the membrane apart to allow the fusion of the viral envelope.
Ø Note: When the CD4 count drops below 200 due to advanced HIV disease, a person is diagnosed with AIDS.
Ø Non-enveloped viruses: entry via clathrin-coated endosomes (endocytosis). Influenza A virus
3. Uncoating: delivers the nucleocapside to the replication site. Marks the beginning of viral replication,
Ø Uncoating is usually achieved by cellular proteases opening up the capsid
Ø When the nucleic acid is uncoated, infectious virus particles cannot be recovered from the cell this is the start
of the eclipse phase, which lasts until new infectious virion are made
4. Biosynthesis: Transcription and protein synthesis:
Ø DS DNA viruses get directly incorporated into the host’s DNA, undergo transcription and translation for
protein synthesis
Ø SS DNA viruses are first converted to DS then undergo the same processes
Ø Positive sense RNA (5’ to 3’): resembles an mRNA, can directly undergo translation,
Ø Negative sense RNA (3’ to 5’): needs RNA dependent RNA polymerase to convert it to a positive sense
strand
Ø DS RNA are transcribed into mRNAs and retroviruses are converted to complementary DNA (cDNA by viral
reverse transcriptase
5. Maturation: The stage of viral replication at which a virus particle becomes infectious; nucleic acids and
capsids are assembled together.
6. Assembly: The stage of replication during which all the structural components come together at one site in the
cell and the basic structure of the virus particle is formed.
7. Release:
Ø Disintegration: naked virus, cause the host cell lysis
Ø Budding: enveloped viruses. Budding viruses do not necessarily kill the cell thus some budding viruses may
be able to set up persistence

Antigenic shift and drift: influenza virus

1. Shift: Causes pandemics. Reassortment of viral genome segments. Can be due to the integration of small
mutations from the host’s genes (even zoonotics)
2. Drift: Causes epidemics. Minor changes based on random mutation in hemagglutinin or neuraminidase genes.

One Health Approach to Global Wellbeing: recognizes the complex interrelationships that exist between people,
animals and the environment as they interact in an era of globalization