Microbiology pavoviruses GROUP 10 PPT final.pptx

Kawalyasteven 39 views 45 slides Oct 12, 2024
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About This Presentation

Pavoviruses microbiology


Slide Content

MICROBIOLOGY 3 GROUP 10 PRESENTATION

GROUP MEMBERS MUGALYA BRIAN VU BPC 2209-1189-DAY MUBUNZE COLLINE MPAMULUNGI CHRISTINE MAYAMBA SANDE MAWANDA ROBERT

Structure and Genomic Characteristics of Parvovirus B19

structure

Parvovirus b19 KEY POINTS Parvoviruses, including B19, are the smallest viruses known to infect and cause human disease. B19 replicates in erythroid precursor cells, causing cell death. Spread is by respiratory, blood and transplacental routes. In healthy individuals, B19 causes immune-mediated rashes (fifth disease, slapped cheek syndrome) and arthropathy. In patients with underlying haematological disease, B19 may result in anaemia or a transient aplastic crisis.

Conti… In immunocompromised patients, chronic anaemia or pure red cell aplasia may ensue. In pregnancy, maternal infection at 0–20 weeks’ gestation may lead to fetal loss or non immunological fetal hydrops. There is no specific antiviral therapy, and no available vaccine for B19

Parvoviruses (parvum means small) have been isolated from a wide range of organisms, and belong to the family Parvoviridae which is divided into two sub families: the Parvovirinae and the Densovirinae . The latter group infects only invertebrates. The Parvovirinae contain five genera: Parvovirus, Dependovirus , Erythrovirus , Amdovirus and Bocavirus Only B19 within the genus Erythrovirus is known to be a human pathogen

Structure and Genomic Characteristics of Parvovirus B19 The name B19 was given because it was first found in the blood of an asymptomatic blood donor (coded 19 in panel B) where it caused a false-positive result in an early test for hepatitis B surface antigen.

Conti… The B19 virion is 20–25 nm in diameter, unenveloped, and contains a single strand of DNA (5.9 kilobase pairs). making it one of the smallest viruses known. Its small size allows it to be transported through the nuclear pore complex into the nucleus for replication Icosahedral Symmetry : It has a highly symmetrical icosahedral capsid made up of 60 subunits. This provides structural stability and protection for its genome.

. There are two capsid proteins , VP1 (minor structural protein) and VP2(major structural protein). VP1 contains additional regions, including a phospholipase A2 (PLA2) domain, which is critical for cell entry and escape from endosomes during infection Terminal Hairpins: The viral genome has palindromic sequences at both ends, forming hairpin structures which aid in the replication of the viral DNA by serving as primers for DNA synthesis once inside the host cell. Receptor Specificity : Parvovirus B19 infects erythroid progenitor cells (precursors of red blood cells) in the bone marrow. It does so by binding to the P-antigen ( globoside ) on the surface of these cells. The virus may also use co-receptors such as integrins (α5β1 integrin) to enhance cell attachment and entry.

Explain the genome of Parvovirus B19 and how its small size influences its replication strategy. Genome and Replication Strategy Small Size: The small size of the Parvovirus B19 genome causes it to have a limited coding capacity. This limitation influences its replication strategy in a couple of significant ways: Dependency on Host Cells : Parvovirus B19 cannot replicate on its own; it requires the host cell's machinery to assist in DNA replication and protein synthesis. Specifically, it needs a host cell that is actively undergoing DNA synthesis, such as in the S phase of the cell cycle.

Cont.. Utilization of Host Resources: Parvovirus B19 exploits host cell polymerases (especially DNA polymerase) for its replication. The virus uses the host's transcription and translation machinery to express its proteins and replicate its genome

Replication Process: Parvovirus B19 employs a unique replication cycle: Entry: The virus enters host cells via receptor-mediated endocytosis, utilizing the erythrocyte P antigen as a receptor, which is abundant on erythroid progenitor cells . . . . . .

Cont.. Nuclear Localization : After entry, the viral DNA is transported to the nucleus, where it must be converted into a double-stranded form (dsDNA) using host cell enzymes. This conversion is crucial because the host's replication machinery primarily acts on dsDNA and nuclear localization suggests that it needs to be actively transported inside the host cell nucleus during viral infection.

How does Parvovirus B19 differ from other viruses in terms of its replication cycle and dependence on host cell machinery?

The Role of Erythroid Progenitor Cells in the Lifecycle and Pathogenesis of Parvovirus B19 Parvovirus B19 is a small, non-enveloped, single-stranded DNA virus known to infect humans. Its pathogenic effects are strongly linked to its specific tropism for erythroid progenitor cells, which are found in the bone marrow. Erythroid progenitor cells are crucial to the production of red blood cells, and the virus’s ability to target and infect these cells is central to the development of several clinical manifestations, particularly anemia-related conditions.

Erythroid Progenitor Cells and Their Role Erythroid progenitor cells originate from hematopoietic stem cells in the bone marrow. As part of the erythropoiesis process, these progenitor cells undergo several differentiation stages, transforming into mature erythrocytes (red blood cells). This process is vital for maintaining an adequate supply of red blood cells, which are responsible for transporting oxygen throughout the body. Parvovirus B19 disrupts this critical process by targeting these cells at a vulnerable point in their maturation, often resulting in anemia.

Mechanism of Targeting Erythroid Progenitor Cells The lifecycle of Parvovirus B19 starts with its entry into the bloodstream. Once in circulation, it has a strong preference for erythroid progenitor cells, particularly those at the proerythroblast stage. These cells express the P antigen (also known as globoside ), a glycolipid receptor that facilitates viral entry. The virus attaches to this receptor, initiating receptor-mediated endocytosis, which allows the viral genome to enter the cell.

Inside the erythroid progenitor cells, Parvovirus B19 exploits the cell’s machinery to replicate its DNA. The virus hijacks the host’s nuclear functions to replicate its genome and transcribe viral proteins. The assembly of new viral particles takes place in the nucleus of the infected cell. As the virus replicates, it eventually causes the infected cell to undergo lysis, releasing newly formed virions into the bloodstream to infect more cells. This lysis of erythroid progenitor cells disrupts erythropoiesis, leading to a decline in red blood cell production.

Clinical Examples of Parvovirus B19 Impact on Erythroid Progenitor Cells Aplastic crisis: In individuals with hemolytic anemia (e.g., sickle cell disease), the virus halts red blood cell production, leading to severe anemia. Fifth disease (erythema infectiosum ): Common in children, self-limiting rash due to immune response. Hydrops fetalis: In pregnant women, Parvovirus B19 infection can lead to fetal anemia, heart failure, and death due to erythropoiesis suppression. Therapeutic Implications Understanding the virus's targeting of erythroid progenitor cells is key to developing treatments. Managing infections involves supporting red blood cell production and addressing immune response. High-risk groups include individuals with hemolytic anemias and immune deficiencies.

Transmission and Epidemiology of Parvovirus B19 Spread is by respiratory, via secretions, like saliva, mucus, or sneezes from an infected person blood transplacental routes/vertical transmission Parvovirus B19 is often linked to outbreaks in schools and daycares because: Close contact in crowded/group settings: Asymptomatic or mild infections in children making it difficult to identify and isolate cases.

Mother to fetus transmission Transplacental infection can occur during acute maternal infection, whether or not symptoms of B19 infection occur in the mother, before maternal antibody has developed and crossed the placenta to protect the fetus. Fetal infection: The virus can infect the fetus by targeting fetal red blood cell precursors

Implications on fetal health Fetal anemia: Parvovirus B19 preferentially infects erythroid progenitor cells in the fetal liver and bone marrow disrupting the production of red blood cells, leading to anemia. Anemia can reduce the fetus's ability to carry oxygen effectively, potentially causing distress or heart failure.

Implications on fetal health Hydrops fetalis In the first 20weeks of pregnancy In severe cases of anemia, the fetus may develop hydrops fetalis, a condition characterized by abnormal fluid accumulation in tissues and cavities (such as the abdomen, lungs, or under the skin). Hydrops fetalis can lead to heart failure and is often fatal if left untreated. -Risk 3%, of which about half die

Cont … intra-uterine death (increased risk 9%) If the fetus develops severe anemia or hydrops, it may lead to miscarriage or stillbirth

Cont …

Global distribution of parvovirus B19 and how the population immunity influences the prevalence of outbreaks Prevalence. - is the proportion of a population who have a specific characteristic in a given time period. -Parvovirus B19 is widely distributed globally, and its prevalence varies by geographical region, age, and socioeconomic status. -The virus is endemic in nearly all countries, with certain populations showing higher seroprevalence rates, especially in areas where the population density is high and where there is a higher incidence of respiratory diseases.

Cont … Seroprevalence. -The percentage of people in a population who have antibodies in their blood that show they have been exposed to a virus or other infectious agent. seroprevalence rates for parvovirus is 60% to 80% in adults across different regions. -This suggests that a significant portion of the population has been exposed to the virus at some point in their lives. Children are particularly susceptible to infection, and seroprevalence tends to increase with age. -Immunity is developed after infection, that is why adults often show higher levels of antibodies against the virus.

Conti… Geographical Variation. a) Developed Countries. - In many developed nations, the rate of infection is high among school-aged children, especially during late winter and early spring when respiratory diseases are more common. b) Developing Countries. - In low-income countries, infections may occur at a younger age due to crowded living conditions and higher rates of viral transmission, but access to healthcare can influence the frequency of observed clinical cases.

. Seasonality . -The virus often exhibits seasonal patterns, with outbreaks typically occurring in late winter and spring. -This seasonality aligns with the circulation of other respiratory viruses, as parvovirus B19 is primarily transmitted via respiratory droplets or through blood High-Risk Populations. - such as individuals with sickle cell disease or other hemoglobinopathies, pregnant women, and immunocompromised individuals, may have a higher burden of disease or complications from B19 infection. -Pregnant women are particularly of concern because an infection during pregnancy can lead to fetal complications, including hydrops fetalis. -Hydrops fetalis is a condition in which there is an abnormal accumulation of fluid in two or more fetal compartments, including the skin, lungs, abdomen, or heart.

. Population Immunity and Its Influence on Parvovirus B19 Outbreaks -The prevalence of parvovirus B19 in a population is influenced by the level of immunity within the population. -Immunity can be achieved through natural infection . NOTE There is no vaccine available for parvovirus B19. - Most individuals acquire immunity after infection, leading to a generally immunized population. Seasonality of Outbreaks. -Outbreaks of parvovirus B19 often exhibit seasonal patterns, with increased incidence observed during specific times of the year, such as late winter and spring. The dynamics of population immunity can amplify these seasonal trends, leading to unpredictable spikes in cases.

. Infection Rates. -Immunity levels within a population can also affect the rate of new infections. A decline in immunity due to lack of exposure can lead to higher rates of infection if an outbreak occurs, as more individuals are susceptible to the virus. Public Health Interventions Monitoring and surveillance are essential to understand the immunity landscape and predict potential outbreaks. Public health strategies focusing on educating high-risk groups and enhancing hygiene practices can mitigate the spread of the virus, especially during outbreak seasons

. Herd Immunity. -In populations where a substantial portion of individuals have been exposed to parvovirus B19, herd immunity can reduce the occurrence of outbreaks. -High levels of immunity in the community can prevent the virus from spreading effectively, thereby reducing the likelihood of outbreak conditions

. Demographic Shifts: -Changes in demographics, such as the age distribution of the population, can influence the prevalence of outbreaks. -For example, if younger generations are less frequently exposed to the virus (due to improved hygiene practices or other factors), they may have lower levels of immunity. This can lead to periodic outbreaks when these individuals come into contact with the virus, especially in settings like schools or daycare centers where the virus is more likely to spread.

. Vulnerable Populations: -Certain populations, such as pregnant women or those with compromised immune systems, are more susceptible to the complications of parvovirus B19 infection. -In communities with high immunity, these populations may be better protected due to reduced overall transmission of the virus.

. Public Health Interventions: -Monitoring and surveillance are essential to understand the immunity landscape and predict potential outbreaks. -Public health strategies focusing on educating high-risk groups and enhancing hygiene practices can mitigate the spread of the virus, especially during outbreak seasons.

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