Lecture 2.4 - Virology and Viral Infections PDF

Lecture 4 Virology and Viral Infection Lecture 4 1  Virology Viruses lack independent metabolism Need a host to replicate Cannot regulate internal conditions (no organelles)...

Lecture 4 Virology and Viral Infection Lecture 4 1  Virology Viruses lack independent metabolism Need a host to replicate Cannot regulate internal conditions (no organelles) Wide range of organisms infected by viruses Lecture 4 2  Virology Cannot react to external factors Do not grow, produced fully formed Very small in size – typically 20-300 nm Generally, very small genomes Lecture 4 3  Viruses and Life Characteristics of life 1. Homeostasis 2. Organisation 3. Metabolism 4. Growth 5. Adaption 6. Response to stimuli 7. Reproduction “Organisms at the edge of life” – Rybicki, 1990 Rybicki, EP (1990). "The classification of organisms at the edge of life, or problems with virus Lecture 4 systematics". S Afr J Sci. 86: 182–186. 4  Viral structure – genome composition Different viruses have different genetic materials Some double stranded DNA Some double stranded RNA Some single stranded DNA Some single stranded RNA Lecture 4 5  Viral structure The genetic material is within the virus There is a protein coat around the genetic material Generally, an outer lipid membrane as well Lecture 4 6  Viral structure The energy required for replication comes from the host The viral particles tend to be highly symmetrical in appearance The virus has some genes – often required for own replication e.g., reverse transcriptase Lecture 4 7  Viral infections Viruses have a VERY limited range of host organisms – often just one species Remember that they only have a limited number of genes – reduces potential for diversity  Mutation required to jump species barrier Lecture 4 8  Viral infections Normally there is a highly specific means of infection Generally linked to site of infection and where the virus will proliferate Potential means of control Lecture 4 9  Viral infection routes Aerosols e.g., measles Faecal-oral e.g., GI tract viruses (Norovirus) Direct contact e.g., sexually transmitted (HIV) Via blood e.g., rabies, Hepatitis B Insect bites e.g., Dengue fever Lecture 4 10  Viral infection factors In addition to ensuring correct infection mechanism, other factors may also be important Temperature range Humidity levels Sunlight (UV) levels Host specific Microbiome Genetic factors Co-morbidities Immune system Lecture 4 11  Viral infection factors For successful infection to occur there needs to be contact with the host Contact must also be with the correct type of tissue e.g., Influenza A virus needs epithelial tissue Lecture 4 12  Viral infection factors There must be some form of recognition taking place Often achieved by use of glycoproteins These react with the cell surface receptors of the host organism Lecture 4 13  Infection events Typically, the pattern shown in this slide will now occur There will be variation depending on the virus involved (e.g., DNA vs RNA virus) Lecture 4 14  Infection events The virus becomes engulfed by the cell The viral coat (capsid) is removed The viral genetic material gets into the nucleus – reverse transcription for RNA Lecture 4 15  Infection events Any expression of viral genes can now take place Replication of viral genome Release of viral genome from nucleus Coating of viral genome to form new mature virus Release of viral particle (killing cell?) Lecture 4 16  Viral taxonomy As with other organisms there is an area of virology devoted to taxonomy Helps to identify the relationship between viruses Lecture 4 17  Human Cytomegalovirus (HCMV) HCMV is classified within the Herpesviridae group Herpesvirus 5 Affects at least half of the population Incidence of infection increases with age Lecture 4 18  Human Cytomegalovirus (HCMV) HCMV is not tissue specific Most tissues can be infected, but mainly salivary glands and leucocytes As with all Herpesviridae, there can be long latent periods Lecture 4 19  HCMV Disease In healthy individuals (particularly adults) most Acute HCMV infection of people are asymptomatic the mouth In immunocompromised individuals problems can occur Colitis Increased susceptibility to other symptoms Acute HCMV retinitis Lecture 4 20  HCMV Disease HCMV is the main cause of retinitis and blindness in patients with HIV In neonates there can be congenital abnormalities following exposure to the virus Lecture 4 21  HCMV Treatment No vaccine is available Antiviral treatments exist Generally, uses Ganciclovir Lecture 4 22  Human Tumour Viruses Some viral infections have been shown to be associated with cancer This generally involved increasing the susceptibility, not guaranteed development Lecture 4 23  Examples of cancer-associated viruses Epstein-Barr Virus (EBV) nasopharyngeal carcinoma Hepatitis B (Hep B) hepatocellular carcinoma Hepatitis C (Hep C) hepatocellular carcinoma Human Papillomavirus (HPV) cervical cancer Herpes virus Kaposi’s sarcoma Human T-lymphotropic virus Type 1 (HTLV-1) adult T cell leukaemia Merkel cell polyomavirus (MCPyV) Merkel cell carcinoma (skin) Lecture 4 24  Zika Virus Zika virus disease (ZVD) transmitted through mosquitoes in the genus Aedes Typically causes mild fever, rash, conjunctivitis Aedes aegypti Lasts around 2-7 days Lecture 4 25  Aedes aegypti (yellow fever mosquito) Aedes aegypti is known to spread the Zika virus It is also involved in spreading: Dengue fever Chikungunya Aedes aegypti Mayaro virus Yellow fever virus Lecture 4 26  Zika Virus No vaccine available No specific treatment Best way to avoid ZVD is to avoid being bitten Found in many tropical/ sub-tropical areas Lecture 4 27  Zika Virus (ZVD) – 2016 outbreak South American Outbreak WHO classified as emergency Linked to Microcephaly Neonatal malformation with small head size Babies may develop epilepsy, learning disabilities, hearing problems, vision problems Many will develop normally Lecture 4 28  Coronaviruses RNA viruses Infect mammals and birds Cause respiratory problems Cross-sectional model of a coronavirus Some very mild, others more severe Long-term effects unknown Responsible for first pandemic since Spanish Flu 1918-1920 Lecture 4 29  Influenza Member of Orthomyxoviridae family 3 species of human influenza; A, B and C (Influenza D infects only cattle) Transmission is airborne from person to person via aerosols Single stranded RNA virus Area of wheel occupied by Uses the negative strand Orthomyxoviridae Lecture 4 30  Influenza Flu viral particles are spherical Approximately 100nm diameter Structures on surface help with infection process: Haemacclutinin (H) – helps with initial attachment Neuraminidase (N) – helps with release of new virus particles Lecture 4 31  Infection by influenza virus The influenza virus infects mucous membranes of respiratory tract Symptoms appear about 1-4 days after inhaling infected droplet Cough and sore throat Low grade fever 2-7 days Chills, fatigue, headache, general aching ~20-30% of infected individuals remain asymptomatic but act as disease reservoirs Lecture 4 32  Recovery and treatment Deaths due to secondary infections are normally in “at risk” groups Global annual figures Around 5-15% of people are get upper respiratory tract infections Typically 3 to 5 million severe cases of influenza Mortality normally about 250,000 to 500,000 people ~ 5% Rapidly recover spontaneously – no antibiotics!! Problems can arise due to secondary infections e.g., Streptococcus pneumoniae infections Lecture 4 33  Treatment of Influenza Rimantidine Tamiflu However, there is now widespread resistance to oseltamivir This occurs through antigenic drift variation in viruses due to mutations in genes encoding antibody-binding sites (more later). Lecture 4 34  Vaccination Vaccination complicated as influenza is genetically fluid 2 factors can contribute to genetic variations drift and shift Drift involves small mutations e.g., point mutations – not normally problem Antigenic shift Two or more strains recombine genes – problem for immune system as these are effectively new Lecture 4 35  Antiviral Therapy Vaccinations are available for many viral conditions Not everyone decides to take up this availability Viral disease Vaccine Antiviral availabilityA Chemotherapy Polio + - Measles + - Mumps + - Rubella + - Hepatitis + + Influenza + (seasonal) + Varicella zoster virus + + Adenovirus/ - - Rhinovirus HIV - + Herpes simplex virus - + Lecture 4 36  Vaccination To work effectively, the level of uptake of a vaccine is normally >95% Where this is not taken up problems can occur Example is for measles outbreak in West Wales in 2012/2013 Lecture 4 37  Vaccination Some vaccination programmes are made available for certain groups of the population Examples include flu vaccinations for certain age groups Lecture 4 38  Geographical isolation as a control The effectiveness of physical barriers may also vary depending on the ability to enforce them. Effectiveness of border controls to limit infection route Lecture 4 39  Ebola as a case study - background Ebola is a virus It exists in animal reservoirs Humans are infected by animals Humans can then infect other humans by transfer of blood and secretions Lecture 4 40  Ebola as a case study - background Some people recover from infection – others die The fatality rate varies, but typically is around 50% Lecture 4 41  Ebola as a case study - background 23rd March 2014 outbreak of Ebola virus disease (EVD) in Guinea Reported by African Regional Office of WHO Worst affected was Guinea However, other countries were affected Lecture 4 42  Ebola as a case study - The worst affected countriesbackground border Guinea However, note that other countries were affected Country Cases Deaths Guinea 5807 2536 Liberia 10675 4805 Sierra Leone 14122 1965 Italy 2 0 Mali 8 6 Nigeria 20 8 Senegal 2 0 Spain 2 0 UK 2 0 USA 4 1 World Health Organization Ebola Statistics – cases and deaths Lecture 4 43  Ebola as a case study – spread of outbreak Outbreak 23rd March 2014 New cases happened on a regular basis 15th September 2015 was the first EVD-free week in Guinea However, that week there were 5 cases in Sierra Leone Lecture 4 44  Ebola as a case study – spread of outbreak 5 cases that week in Sierra Leone 4 of these cases had registered contact with previously affected individuals – all in area shaded in brown Fifth case was in Bombali (yellow area) No obvious links to the Bombali case Lecture 4 45  Ebola as a case study – spread of outbreak The example in Bombali was a 16-year- old girl who was showing severe symptoms for several days She was isolated immediately in an Ebola treatment centre Rapid-response treatment team deployed to minimise risk of more spread Lecture 4 46  Ebola as a case study – possible problems Not everyone obeys the restrictions imposed Example of man who fled from Aberdeen in the Freetown area of Sierra Leone Probably source of spread http://www.who.int/ebola/publications/nejm-after- ebola.pdf?ua=1 Lecture 4 47  Control of outbreaks 1. Isolation and quarantine 2. Treatment and vaccination 3. Public health interventions 4. Health education and communication 5. Enhanced surveillance 6. Environmental alterations Lecture 4 48  Thank you Lecture 4 49