Virus Virulence PDF

Virus Virulence Dalina Yusoff Fakulti Farmasi UKM  R0 = reproduction number How contagious an infectious disease is  R0, R’naught’ A mathematical term that indicates how contagious an infectious disease is. It’s also referred to as the reproduction...

Virus Virulence Dalina Yusoff Fakulti Farmasi UKM  R0 = reproduction number How contagious an infectious disease is  R0, R’naught’ A mathematical term that indicates how contagious an infectious disease is. It’s also referred to as the reproduction number. As an infection is transmitted to new people, it reproduces itself. A disease’s R0 value only applies when everyone in a population is completely vulnerable to the disease. This means: – no one has been vaccinated – no one has had the disease before – there’s no way to control the spread of the disease What conditions Infectious period Contact rate are measured by Mode of transmission R0?  Viral virulence Virulence : the capacity to cause disease in infected host. Mild-to-lethal effect. Viral virulence Capacity of a virus to cause a disease in a host. Virulent vs Avirulent or attenuated virus Virulence can be quantitated: – Mean time of death – Mean time to appearance of symptoms – Measurement of fever, weight loss – Measurement of pathological lesions (poliovirus); reduction in blood cd4 cells (HIV) Influenced by dose, route of infection, species, age, gender and susceptibility of host. Cant compare virulence of different viruses. For similar viruses, assays must be the same.  Major goal of virology Virus virulence genes Identifying is to identify viral and that affect: host genes that Virus replication virulence determine virulence. Invasiveness Virulence genes genes usually identified by Tropism mutation: a virus that Modify host defence causes reduced or no mechanism disease in a specified Enable the virus to system. spread in the host Intrinsic cell killing effects Genes products that alters the ability of virus to replicate  The spectrum of tissues infected by a virus. – Enterotropic, neurotropic, hepatotropic Tissue Ranges from limited to pantropic Tropism Some determinants: susceptibility, permissivity, accessibility, defense  Human influenza virus Tryptase to cleave HA upon release Produced by club cells in respiratory tract TMPRSS2 (transmembrane protease serine 2), endosome transmembrane protease, cleaves during entry Tissue tropism Avian H5N1 virus Infect many cells other than respiratory tract HA protein has furin cleavage site Cleaves by furin, ubiquitous in cells.  Spike protein attach to ACE2 receptors Spike genome sequence reveales TMPRSS2 and SARS CoV-2 furin cleavage site, not seen in SARS CoV 1 Viral tropism not restricted to respiratory tract  Virus cause immunosuppression They can globally reduce the immune response while they are infecting Mechanisms: – Replication in one or more cells of the immune system (HIV) – disturb cytokine production and intracellular signaling – Viral proteins acting as viroceptors or virokines (immune modulators)  Mechanisms of cell injury by viruses Cytolytic viruses: cytopathic effects (apoptosis, necrosis, pyroptosis) Viroporins Viral inhibition of host proteins and RNA synthesis, leads to loss of membrane integrity, leakage of enzymes from lysosomes, cytoplasmic degradation Syncytium formation by enveloped viruses: parainfluenza, HIV  Other determinants of virulence Age: Very young and very old humans most susceptible to disease – Young- immaturity of immune response; greater freedom from immunopathology – Old – less elastic alveoli (smokers), weak respiratory muscles, diminished cough reflex Gender: male slightly more susceptible to viral infections than females Pregnancy: hep A, B, E, influenza more lethal, polio more common Malnutrition increases susceptibility because physical barriers and immune response are compromised. – for this reason, measles is 300x more lethal in dev countries than Europe, north America. Cigarette smoking Stress - HSV