Viral Pathogenesis - NUR 3107

VIRAL PATHOGENESIS NUR 3107 Professor Dr. Chee Hui Yee Name the viruses that you know?  Viruses Are infectious agents with both living and non-living characteristics : Living – replicate fast but in a living host cell, can mutate Non-living – acellular, no cytoplasm or ce...

VIRAL PATHOGENESIS NUR 3107 Professor Dr. Chee Hui Yee Name the viruses that you know?  Viruses Are infectious agents with both living and non-living characteristics : Living – replicate fast but in a living host cell, can mutate Non-living – acellular, no cytoplasm or cellular organelles, replicate using host metabolic machinery  History - Virus was first described in 1900s based on the disease or the symptoms it cause. - Viruses that cause liver pathology were grouped together as hepatitis virus  History - In 1930s development of electron microscopy permitted the detail descriptions of virion morphology In 1966 - International Committee on Taxonomy of Viruses (ICTV) formerly known as ICNV was established to classify and name viruses https://ictv.global/  Taxonomy - Order – Family – Subfamily – Genus – Species – virus name -Example: Mononegavirales – Pneumoviridae – Pneumovirinae – Orthopneumovirus – Human orthopneumovirus - human respiratory syncytial virus  Taxonomy - Order – Family – Subfamily – Genus – Species – virus name -Example: Nidovirales – Coronaviridae – Coronavirinae – Betacoronavirus – Severe acute respiratory syndrome-related coronavirus - severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)  Taxonomy - Order – Family – Subfamily – Genus – Species – virus name -Example: Chitovirales – Poxviridae – Chordopoxvirinae – Orthopoxvirus – Monkeypox virus - Monkeypox virus Naming of virus  Naming of virus Examples: Ebola Virus (Ebola - name of a river) Nipah Virus (Nipah – name of a village) Melaka Virus (Melaka - name of a state) Japanese Encephalitis Virus (Japanese - A ✓ nationality) Severe Acute Respiratory Syndrome Coronavirus 2  Viral pathogenesis Consequences of a viral infection depend on a number of viral and host factors Host responses causing asymptomatic infections, induction of various cancers, chronic progressive neurological disorders and possible endocrine diseases  Cellular and viral factors in pathogenesis Types of cells – poliovirus multiply in nervous tissue but not in kidney of a living monkey Maturation of cells – virus more virulent in newborn Genetic factor of the host - Viruslife cycles - Host-cell interaction - Immune response Virus Life Cycles Infection starts with virus attachment, entry, uncoating, replication, assembly, transport and release of virus progenies from infected cells  1. Attachment Virus must absorb or attach onto susceptible host cells. This interaction happened on the surface of both the virus and host cells. The interaction is specific. molecule on virus – virus attachment protein/molecule (VAP) molecule on host cells – receptor Binding of both molecules is through multivalent interaction  2. Penetration - Energy dependent 1. Plasma membrane fusion 2. Endocytosis 3. Translocation  Plasma membrane fusion - pH independent - Only enveloped virus can use Endocytosis - Most virus using this process - Non-enveloped and enveloped virus - pH dependent pathway Translocation Genomic material directly released into cytosol 1. Translocation (non-enveloped) 2. Genome injection 3. Endocytosis (non- enveloped) 4. Endocytosis and membrane fusion (enveloped) 5. Membrane fusion (enveloped)  3. Virus uncoating Removal of envelope or capsid protein to release the viral genome for replication Energy dependent Locations: 1. At plasma membrane 2. Within an intracellular vesicle 3. In the cytosol 4. At nuclear membrane 5. In the nucleus 3. Virus uncoating 3. Virus uncoating  4. Genome replication As a rule, DNA viruses replicate within the nucleus while RNA viruses replicate within the cytoplasm. Exceptions are: poxviruses (DNA viruses) replicate within the cytoplasm and orthomyxoviruses and hepatitis D virus (RNA viruses) replicate within the nucleus.  Genomic Material -DNA or RNA (either one not both) -DNA – Double-stranded DNA Single-stranded DNA RNA - Double-stranded RNA +ve-sense single-stranded RNA -ve-sense single-stranded RNA Segmented or non-segmented The Baltimore Classification -Depending on the nature of its genome: -RNA viruses - 8 strategies: Dengue virus, SARS-CoV-2 virus, Nipah virus, Influenza virus, Hanta virus, Rotavirus, HIV, Hepatitis delta virus -DNA viruses – 4 strategies: Adenovirus, Pox virus, Parvovirus, Hepatitis B -Dengue virus: +ve single-stranded RNA coding for one genome-size mRNA synthesis minus strand RNA +ve strand RNA SARS CoV-2 virus: +ve single-stranded RNA coding for one or more subgenomic mRNA synthesis minus strand RNA +ve strand (full size or different sizes of subgenomic mRNA)  5. Assembly - Packing the genome with the capsid protein. - For enveloped viruses, envelopment will occur to produce mature virion - Assembly site: 1. cytoplasma - Poliovirus 2. nucleus - Adenovirus 3. plasma membrane – Influenza A virus 6. Transportation  6. Release Process depends on the structure of the virus - Budding – enveloped viruses - Exocytosis - enveloped viruses - Lytic – most non-enveloped viruses Virus replication cycle Dengue virus Ebola virus Virus replication cycle (non enveloped virus)  Outcome of Viral Infection Acute Infection Recovery with no residue effects Recovery with residue effects e.g. acute viral encephalitis leading to neurological sequelae. Death Proceed to chronic infection  Outcome of Viral Infection ◼ Chronic Infection ◼ Silent subclinical infection for life: Cytomegalovirus (CMV), Epstein–Barr virus (EBV) ◼ A long silent period before disease: Human immunodeficiency virus (HIV) ◼ Reactivation to cause acute disease: Herpes simplex virus (HSV) ◼ Chronic disease with relapses and exacerbations: Hepatitis B virus (HBV), Hepatitis B virus (HCV). ◼ Cancers: EBV, HBV, HCV, Human papillomavirus (HPV), Human Herpesvirus-8 (HHV-8)  Immune Response The immune response to the virus has greatest impact on the outcome of infection If the virus is cleared, results in complete recovery If the virus is not cleared, results in persistent infection  Immune Response Immune response plays a major pathological role in the disease Cellular immunity plays the major role in clearing virus infection T cell – kill the infected cells Humoral immunity protect against reinfection – neutralize virus IgM – test for acute infection IgG – past infection  Foodborne and waterborne Viruses Hep A virus, Norovirus (Norwalk-like virus), Rotavirus, Hep E virus, enterovirus, adenovirus Type of food? Shellfish – mussels, oyster, clams, cockles  Transmission Enteric (Fecal-oral) route Virus shed in fecal, vomitus and contaminated the water then shellfish filter the water and virus enter the shellfish Contamination by food handlers  Detection Hep A – incubation period can up to 6 weeks after consuming contaminated food Norovirus – 24-36 hours of incubation period Testing the present of the virus in fecal or blood by TEM, antigenic specificity and genetic amplification Zoonotic Diseases A disease transmitted from ANIMAL to HUMAN https://proveg.com/blog/zoonotics-pandemics-viruses-animals-and-humans-in-a-globalised- world/ - 2020 https://proveg.com/blog/zoonotics-pandemics-viruses-animals-and-humans-in-a- globalised-world/ - 2020  Zoonotic Virus outbreaks Year Outbreak Common Disease Virus Death Remarks area name Smallpox Smallpox 1518－1568 Maxico 17Mil 1556－1560 HIV–42.3 Mil death Europe Flu virus IV 25 Mil 1st Flu, 20% mortality 1775－1782 since 1981 North America Smallpox Smallpox virus 130K 1918－1919 World Spanish Flu Flu IVA H1N1 25 Mil The end of WW1 Vaccine 1957－1958 World Asian Flu Flu IVA H2N2 2 Mil development Hong Kong 1968－1969 World Flu IVA H3N2 750K Flu IVA H1N1 2009－2010 World Swine Flu Swine Flu 14K mutant H5N1  H5N1 https://theconversation.com/bird-flu-is-hitting-australian-poultry-farms-and-the-first- human-case-has-been-reported-in-victoria-heres-what-we-know-230691 H5N1  Epidemic / Pandemic virus Swine influenza virus A H1N1 – 2009 Avian influenza virus A H7N9 – 2013, 2019 Avian influenza virus A H5N1 – 2017 Swine influenza virus A H1N1 and B – 2019-2020 What had happened to the Avian?  Emerging virus Ebola virus – 2014 Rabies virus – 2018 Monkeypox Virus – 2019 & 2022 Measles virus - 2023 Dengue virus – 2023-2024 Oropouche virus – 2024 Marburg virus - 2024 Rabies Virus Monkeypox virus (2019) Monkeypox virus (2022)  Severe condition Monkeypox Smallpox  Marburg virus is a highly fatal viral hemorrhagic fever (VHF) that is spread through contact with an infected person's body fluids or an infected animal. The virus is maintained in nature in Egyptian fruit bats, but can also infect nonhuman primates. Human infections are often associated with exposure to bats in caves or mines. Outbreaks can also occur when infected monkeys are imported. Marburg virus is not spread through the air.  New virus Nipah Virus – 1999 SARS Coronavirus – 2002-2003 MERS Coronavirus – 2012 SARS-CoV-2 (COVID-19 virus) – 2019 - ?  What is the transmission mode of zoonosis diseases? Respiratory droplet Close contact Blood or other body fluids Animal bite (saliva) Consuming contaminated meat/meat products Global Virome Project Ravage populations 600K-800K viruses are potentially zoonosis and bats have >200 viruses  Emerging virus Arbovirus Dengue virus – 2023-2024 Oropouche virus – 2024 Dengue Virus Oropouche virus disease is transmitted (spread) to humans mainly through the bite of an infected midge (Culicoides paraensis) which primarily bites around dawn and dusk.  Emerging virus Vaccine-preventable virus Measles virus – 2023 Polio virus Measles Virus  Measles Virus The data reflected covers September 2023 - February 2024. Measles Virus  Polio Virus Wild poliovirus type 2 was eradicated in 1999, and type 3 was eradicated in 2020. Wild poliovirus type 1 is still endemic in Afghanistan and Pakistan. Polio is still a risk in communities with low vaccination rates, poor sanitation, and disrupted healthcare. Outbreaks of vaccine-derived poliovirus (VDPV) have occurred in areas with low vaccination rates. The risk of polio can be especially high for children in war and conflict zones.  Polio Virus There are two vaccines available: oral polio vaccine (OPV) and inactivated polio vaccine (IPV) OPV is made from a weakened live polio virus In Malaysia, OPV has been completely switched to IPV in the national immunisation program since 2010. IPV has mixture of inactivated, killed strains of all three poliovirus types.  Prevention and treatment Vaccine – prevent infection for human virus Live-attenuated, killed viruses, virus proteins (subunit), vector-based, mRNA Antiviral drug – nucleoside analogues – virus incorporate into its genome during replication. The life cycle of the virus is halted  Today’s Message When we make changes, we are saving ourselves; when we can influence others, we are saving others.