IMMS Viruses.
Basics
Replication (Where they cause problems!)
1. ATTACHMENT – viral and cell receptors e.g. HIV (gp120 and CD4).
2. CELL ENTRY - only central viral ‘core’ carrying the nucleic acid and associated proteins enter the
cell cytoplasm.
3. INTERACTION with HOST CELLS – use of cell materials (enzymes, amino acids, nucleotides) for
viral purposes; subversion of host cell defence mechanisms.
4. REPLICATION -may localise in nucleus, cytoplasm or both; production of progeny viral nucleic
acid and proteins.
5. ASSEMBLY - may occur in nucleus e.g. herpesviruses, in cytoplasm e.g. enterovirus, or at the
cell membrane e.g. influenza virus.
6. RELEASE -by bursting open (lysis) of cell e.g. rhinoviruses; or by ‘leaking’ (exocytosis) from the
cell over a period of time e.g. HIV, influenza virus.
They cause disease by:
Destroying the host cells (HIV)
Modifying the host cell structure (Rotavirus)
Over reactivity of the host (Hep. B/C)
Cell proliferation and immortalisation, ie, causing cancer (HPV)
They can be very persistent, be very changeable and some can even modify the host’s defences,
causing release of interferon and cell apoptosis. All of these factors can make them very tricky to kill!
Our Defenses
Interferons are cytokines, acting as messengers between cells of the immune system. There are
several types of interferon, including:-
a- and b-interferon - produced by all nucleated cells during a viral infection, inducing an antiviral
state in neighbouring cells.
g-interferon (‘immune’ interferon) - produced by subsets of T lymphocytes and natural killer (NK)
cells. Has pivotal role in the control of specific immune responses.
Viruses can inhibit the production of this – Hep C Virus is very good at blocking the RIG-1 gene in
hepatocytes, and therefore reduces production of interferon.
Respiratory Viruses
80% sore throats viral, most often adenovirus.
Influenza A
Myxovirus, RNA, enveloped
RNA coating in 8 segments
4 major proteins
o Haemagglutinin (H) – 4 types
o Neuraminadase(N) – 7 types
o Matrix (M)
o NeucleoProtein(NP)
Causes Influenza – Fever (essential for
diagnosis), sore throat, body- ache, chills.
Incubation period is 24-48 hours.
Epdemic – Caused by minor antigen changes in H
and N, referred to as drift. With ‘flu, this tends to happen in winter for normal (seasonal)
‘flu.
Pandemic – Caused by a major change in the antigens, referred to as shift. Major changes
occur when the genetics are reasserted during dual infection, for example, pigs.
Treatment should be started within 48hrs of the beginning of symptoms.
o Neuraminadase Inhibitor antivirals used or prophylaxis
o Zanamavir (Relenza)-inhaled
o Oseltamivir (Tamiflu)-oral
Herpes Viruses
I think that there are 8, but the slides are not as clear as I would have hoped.
Herpes Simplex (1&2) Causes cold sores orally and genitally. Spread by direct contact with
sores. Cannot be truly eliminated, as causes a latent infection in nerves as well as the
chickenpox rash – will float around undetected and asymptomatic because the DNA is silent
and doesn’t produce any proteins, but can cause symptoms when it starts to replicate.
Varicella Zoster (3) Causes chicken pox and shingles (over compensatory immune response
that can flare up when reinfected).
o Spread by droplets and direct contact.
o Shingles will track the direct route of the root ganglion that is infected – can cause
nerve damage.
1-3 are all treated with Aciclovir or Valaciclovir, orally or (acyclovir) IV.
Cytomegalovirus (4)
o causes very few symptoms, mainly flu like, but will not go away, only lie dormant.
o Reinfections are usually fairly asymptomatic, but if the patient is immunosuppressed
(HIV or after transplant) and can cause symptoms such as mouth and oesophageal
ulcers; visual ‘floaters’; retinitis; hepatitis and pneumonia along with other flu like
symptoms.
o Can also affect newborn babies, presenting with enlarged liver and spleen; jaundice;
pneumonia; purple rash and seizures .
o Tends to be treated with Ganciclovir
Epstein-Barr Virus (5)
o Glandular Fever! Pyrexia (over 38oC), sore throat, swollen glands in neck, fatigue.
o No real cure, just bed rest, careful observation and avoid contact sports, as spleen
can burst!
o 1-2 month incubation, spread through saliva (Kissing!)
o Inhibits apoptosis of B-lymphocytes, as they can only survive in the cells.
6-8 are not mentioned on the slides, but 6 and 7 can cause a rash and temp in children
(roseola) and 8 only infects HIV and immunocompromised patients, causing Kaposi
Sarcoma.
Hepatitis - Can be an acute infection or can progress to chronic hepatitis, cirrhosis and
hepatocellular carcinoma. Test for b/c anitgen or IGM for a&e.
Hepatitis A-enterovirus Faecal-oral spread
Hepatitis B- hepadnavirus Parenteral(blood borne)
Sexual
Vertical (mother to baby at birth)
Hepatitis C-flavivirus Parenteral (blood borne)
Hepatitis E-calicivirus Faecal oral (water borne)
Acute infections tend to be self resolving, but supporting treatment may be required, eg
analgaesia. Chronic infections tend to be treated with interferons for both B and C, or a
combination of antivirals. This includes lamivudine, tenofovir, entecavir, and adefovir ( after a
few years, the virus may develop a resistance to some of the antivirals, eg 60% of cases become
resistant to lamvudine after 3 years) for hep B and Ribavirin for hep C.
Rashes
Paramyxovirus – Measles.
The virus can spread directly from cell-to-cell forming ‘syncytia’ – groups of infected host
cells fused together through the action of the MV fusion protein.
Upper Respiratory tract infected, but can cause LRT infections. Look out for febrile
convulsions and giant cell pneumonia in some cases. Can also cause a secondary pneumonia
– antibiotics sometimes given as prophylaxis.
Togavirus – Rubella. Look out for infection in pregnant women, as can cause foetal abnormalities.
Parvovirus B19 (Erythrovirus) causes Erythema Infectiosum/Fifth Disease/ slapped cheek syndrome,
presenting with characteristic rash, pyrexia and myalgia. Can cause haemolytic aplastic crisis (no
rbc!) in immunosuppressed individuals or anaemia. Bad in pregnancy. No treatment.
HIV
Infects CD4 cells.
Can form several mutations and quasi species, which make it very hard for the body to fight.
Can also lie latent for months without causing any symptoms.
