Week 8 Flashcards
Viruses
Sub-microscopic, obligate intracellular parasites
With no cell nucleus, organelles or cytoplasm
That only replicate inside a living host cell using host metabolic machinery and
ribosomes to form components that can be assembled into virions
Virus Particle (or Virion)
DNA or RNA (single or double stranded)
And a protein coat or capsid (+/- envelope)
This is the extracellular form that enables a virus to be transmitted from one host
cell to another and is metabolically inert
Classification of Viruses
Shape (symmetry)
Type of nucleic acid (Baltimore classification)
Whether they have an envelope
What they infect
Viruses are either naked or enveloped
Envelopes are membranous structures surrounding the nucleocapsid and are common for animal viruses. The envelope is a lipid bilayer (derived from the
host cell membrane) and has mostly virus-encoded proteins (usually
glycoproteins) embedded in it.
In the case of an enveloped virus, symmetry refers to the nucleocapsid
inside the virus and not the whole virion shape
Genetic Classification (Baltimore)
Class I: The double-stranded DNA viruses, Herpesvirus
Class II: The single-stranded DNA viruses, Parvovirus
Class III: The double-stranded RNA viruses, Rotavirus
Class IV: The single stranded coding (+) sense RNA viruses, Poliovirus
Class V: The single stranded anti-coding (-) sense RNA viruses, Influenza virus
Class VI: The single stranded (+) sense RNA viruses using DNA intermediate, Retroviruses
Class VII: The double stranded DNA viruses using RNA intermediate, Hepatitis B virus
General features of viral replication
- Attachment
- Penetration
- Synthesis of nucleic acid and protein
- Assembly and packaging
- release
Virus Receptors
These receptors carry out normal functions for the cell but the virus exploits
these receptors for its own advantage (attachment and penetration). These
receptors determine which cell types can be infected.
Outcomes of viral infection
Transformation of normal cells
lytic infection
persistent infection
latent infection
Human Immunodeficiency Virus
HIV belongs to the Lentivirus genus of the family Retroviridae
HIV: transmission
HIV is transmitted through:
• Sexual contact (any type of unprotected sexual contact)
• Blood (e.g. sharing needles, blood transfusion)
• Mother-to-child (vertical transmission)
HIV: Early during infection there may be a flu-like illness
• Fever, headache, tiredness, enlarged lymph nodes, occurring 1-2 months post exposure, lasting 1-4 weeks
• Highly infectious at this time, the infected individual may not be sero-positive
HIV: Asymptomatic period
• Lasts from months to >10 years
• Virus is still actively multiplying and infectious; T cell numbers are slowly decreasing
HIV: AIDS
AIDS:
• CD4 T cells decrease to <200/mm3 (healthy adults have >1000)
• Opportunistic infections occur (e.g. organisms that do not normally cause disease in healthy people)
• If untreated, the average time to death without treatment is 11 years
How does HIV cause disease?
• CD4+ T-cells are key to the immune response by stimulating other immune cells, such as
macrophages, B-cells, and CD8+ cytotoxic T-cells, to fight infection
• During the acute phases of the infection, HIV may eliminate more than half of the host’s gut resident
CD4+ T cells which express CCR5
• As a result, “microbial translocation” may occur with leakage of gut microbes and their products
across the tight epithelial barrier and into circulation leading to inflammation and pathogenesis
• Peripheral CD4+ T cells are also infected resulting in HIV turnover and the depletion of CD4+ T-cells
over time
• The depletion of CD4+ T cells causes immune deficiency and increased susceptibility to infection by a
range of pathogens
Opportunistic Diseases in AIDS
• Kaposi’s Sarcoma - cancer of the cells lining blood vessels characterised by purple
patches on the skin surface - caused by human herpesvirus 8 (HHV8)
• Pneumocystis carinii pneumonia
• Mycobacterium spp infections e.g. tuberculosis
• Histoplasmosis
• Candiadiasis
• Cytomegalovirus (CMV) disease
Influenza
Is an enveloped, negatively-sensed RNA virus with a segmented genome
Virions can appear spherical or filamentous
Influenza Virus Types
Types A, B, C and D
Most disease in humans is caused by Influenza A followed by Influenza B
Influenza C can cause mild illness in humans but not epidemics, while Influenza D
primarily affects animals, in particular, cattle
Influenza virus replication (in depth)
Influenza enters the host cell by HA binding to sialic
acid on glycoproteins on the host cell.
The host cell endocytoses the virus, which then fuses
its envelope with the endosomal membrane.
The nucleocapsid is released into the cytoplasm, then
travels to the host nucleus where primary transcription
of the viral genes by the viral RNA polymerase occurs.
Once the viral mRNAs are transcribed, they are exported
out of the nucleus to the cytoplasm and are translated by
host cell ribosomes to synthesize new viral proteins
Newly synthesized viral polymerase and nucleoproteins proteins are imported back into the nucleus to
increase the rate of viral replication.
Influenza virus replication (simplified)
Attachment (adsorption)
Penetration
Uncoating
Viral protein synthesis
Viral nucleic acid replication
Virus assembly
Viral release
Influenza symptoms and incubation
The incubation period is 1-4 days.
Patients are infectious from the day before symptoms begin until approximately 5 days after onset.
SYMPTOMS INCLUDE:
high fever, myalgia headache, malaise cough,
sore throat, rhinitis
Influenza antivirals
Neuraminidase (NA) inhibitors such as Tamiflu block the ability of NA to cleave Haemagglutin (HA).
Antigenic drift
The virus can mutate and make new antigenic variants of
HA and NA (antigenic drift).
Influenza Virus Nomenclature
Virus
type
Place of
isolation
Host of
isolation
Isolate
number
Year of
isolation
HA and NA
Subtype
Global impact of Pandemic Influenza
• 1918 “Spanish Flu” (H1N1): approx 50 million deaths est. (CDC)
• 1957 “Asian Flu” (H2N2): approx 1.1 million deaths est. (CDC)
• 1968 “Hong Kong Flu” (H3N2): approx 1 million deaths est. (CDC)
• 2009 “Swine Flu” (H1N1): 151,700-575,400 deaths est (CDC)
Seasonal influenza
290,000 to 650,000 respiratory
deaths worldwide annually (WHO)
