Microbiology: A Clinical Approach © Garland Science CHAPTER 13 VIRAL PATHOGENESIS © CNRI / Science Photo Library

WHY IS THIS IMPORTANT? Most infections are caused by viruses. Health care professionals must understand the pathogenic mechanisms used by these pathogens.

PATTERNS OF VIRAL INFECTION Viral infections can be: Acute (rapid and self limiting) Persistent (long term) Latent (extreme versions of persistent infections) Slow or transforming (complicated types of persistent infections)

PATTERNS OF VIRAL INFECTION Cytopathic viruses produce virions and kill host cells rapidly (cytopathology). Noncytopathic viruses produce virions but do not cause cytopathology. Some viruses do not produce virions or cause cytopathology but still cause infection.

PATTERNS OF VIRAL INFECTION Incubation periods vary for different viruses. Some are as short as days. Some are as long as years. During the incubation period: The virus is replicating. The host is beginning to respond

PATTERNS OF VIRAL INFECTION

Microbiology: A Clinical Approach © Garland Science ACUTE INFECTIONS

Acute viral infections are severe public health problems. They are usually associated with epidemics. The main problem is the short incubation period. This causes a delay in identifiable symptoms until the virus has already spread. Acute infection epidemics are often seen in crowded populations. Schools Military bases and Nursing homes

DISSEMINATION AND TRANSMISSION OF VIRAL INFECTION Viral infections are disseminated within the host and transmitted from one host to another. There are three basic requirements for successful infection: Sufficient number of viruses present The number depends on the type of virus, the site of infection, and the age and health of the host. Access to susceptible and permissive host cells An ineffective host immune response

VIRAL DISSEMINATION The three main entry points are: Respiratory system Digestive tract Urogenital tract The most common portal of entry into the human body. It is always exposed to large numbers of potential pathogens. Viruses easily disseminate from here into other areas of the body.

Microbiology: A Clinical Approach © Garland Science VIRAL DISSEMINATION: Urogenital Tract © SOA-AIDS Amsterdam

Microbiology: A Clinical Approach © Garland Science VIRAL DISSEMINATION: Other Portals of Entry © CDC/ Dr. K. L. Hermann

VIRAL DISSEMINATION: Skin Some viruses enter through the skin. Usually by vector transmission from biting insects If they remain in the epidermis, a localized, acute infection occurs. If they get into the dermis, a systemic infection can occur.

VIRAL DISSEMINATION: Nervous System Some viruses can enter the body through the nervous system. They can disseminate throughout the entire body. Some target neurons. Some use neurons to get to their preferred target area.

VIRAL DISSEMINATION: Organs Viruses released from the apical surface host cells cause localized limited infection. Viruses released from the basement membrane of host cells can spread systemically. The bloodstream is the best route for systemic viral infection. Referred to as hematogenous dissemination Viremia refers to virus replicating in the blood

VIRAL TRANSMISSION Viral transmission refers to the spread of the virus from one host to another. There are two patterns of viral transmission: Transmission within a single species Human to human. Transmission between species Animal to human

VIRAL TRANSMISSION Viruses can be transmitted in several ways: Via inanimate objects Via poor techniques employed by health care workers: This type of transmission is referred to as iatrogenic transmission. Fecal-oral route – the digestive tract

Microbiology: A Clinical Approach © Garland Science VIRAL TRANSMISSION © Kent Wood / Science Photo Library

VIRULENCE There are three ways to measure viral virulence: LD 50 – how much virus is required to kill 50% of a subject population ID 50 – how much virus is required to infect 50% of a subject population PD 50 – how much virus is required to paralyze 50% of a subject population.

VACCINE DEVELOPMENT There are three groups of vaccines: Live attenuated vaccine –made of intact virions rendered non-infectious Inactivated or killed vaccine – composed of killed or dead virions Subunit vaccine – composed of immunogenic parts of virions.

VACCINE DEVELOPMENT Vaccination causing immunization can be either active or passive. Active immunization – antigen is administered and causes the onset of the immune response Passive immunization – a preformed antiviral product, such as antibody, is administered.

VIRUSES AND CANCER Some viruses can cause cancer in animals. An estimated 20% of human cancers involve viruses. Retroviruses can inactivate genes responsible for suppressing tumor formation. Viruses associated with human cancers include: Epstein-Barr virus Hepatitis B and C viruses HPV

Viruses and Cancer Mechanism of cancer causation 23

Common Viral diseases: A.Influenza Properties: Member of the Orthomyxovirus family Enveloped RNA virus Packaged into helical nucleocapsids Antigenic variation & genetic exchange lead to the appearance of new strains; requires use of different vaccine combinations each year

….Influenza Symptoms & Complications of Influenza: Respiratory Tract Symptoms Fever Neurological Complications: Guillain-Barré Syndrome Reye’s Syndrome

B.Diseases Caused by the Herpes Family Properties of the Herpes Virus Family: Large, enveloped DNA viruses Icosahedral capsids ( regular polyhedron with 20 identical equilateral triangular faces, 30 edges and 12 vertices. DNA replicates in the nucleus of host cells Cells may become permanently infected Host chromosomes may be altered Herpes infections associated with certain cancers

…Diseases Caused by the Herpes Family Herpes Simplex: Two major strains Type I: Oral Herpes Type II: Genital Herpes Skin lesions form at site of the infection Virus travels along sensory neurons to ganglia, where it remains During times of stress or weakened immunity, virus may travel along same neurons to re- infect the initial skin sites

Oral herpes- infects the face and mouth. The visible symptoms of which are colloquially called cold sores or fever blisters, infects the face and mouth.

Genital herpis Genital herpes- known simply as herpes

…. Herpes Simplex (cont.) Other complications with Herpis simplex: Herpes encephalitis- inflammation or infection of the brain and central nervous system (CNS). Congenital herpes-birth-acquired herpes is a herpes virus infection that an infant gets (acquires) at the time of birth Cervical cancer –cancer of the cervix Bell's palsy is a dysfunction of cranial nerve VII that results in inability to control facial muscles on the affected side (Check images of Bell palsy) Treatment: Acyclovir ( Antiviral medicine)

…..Diseases Caused by the Herpes Family Chicken pox & Shingles: Cause: Varicella-zoster virus Chicken pox symptoms –rashes (Check images) A rash appears on the skin on the first day of the disease. Tiny red spots on the skin, mostly on the upper back or chest. In severe cases, a rash may appear on the face and lower extremities. The papules turn into blisters and finally become pustules and form scabs, which fall off Treatment -Chicken pox vaccine

Shingles: The chickenpox virus reactivates and causes shingles ( Check images) Early symptoms of shingles include headache, sensitivity to light, and flu-like symptoms without a fever

….Diseases Caused by the …Herpes Family Infectious mononucleosis Disease Cause: Epstein-Barr virus (EBV) Infectious mononucleosis, or "mono“ Also called as human herpes virus 4 (HHV-4), is a possible, but not scientifically proven, cancer causing virus of the herpes Lymph node swelling; fever; fatigue (check images) The virus spreads through saliva, which is why it's sometimes called "kissing disease.“ Mono occurs most often in 15 to 17-year-olds

Monotest Mononucleosis tests are blood tests to look for antibodies that indicate mononucleosis (mono) caused by EBV The antibodies are made by the immune

….Diseases Caused by the Herpes Family Cytomegalovirus Congenital CMV ( present at birth) or cytomegalovirus (Check images) CMV is the most common virus transmitted to a pregnant woman's unborn child, person to person, through close contact with body fluids (urine, saliva (spit), breast milk, blood, tears, semen, and vaginal fluids Mild symptoms in healthy individuals

.. Cytomegalovirus CMV Approximately 1 in 150 children is born with congenital CMV infection Miscarriages when contracted during pregnancy Severe infections in AIDS patients Major cause of blindness in AIDS patients No vaccine currently…preventive

SummaryHERPES VIRUS TYPES THAT INFECT HUMANS Herpes simplex virus Type 1 (HSV-1) Herpes simplex virus Type 2 (HSV-2) Epstein Barr virus (EBV) Cytomegalovirus (CMV) Varicella Zoster Virus (VZV) Human herpes virus 6 Human herpes virus 8 Once a patient has become infected by herpes virus, the infection remains for life

Viral Hepatitis Hepatitis A: Also known as: Infectious hepatitis Short-incubation hepatitis Viral Properties: Picornavirus Family Small nonenveloped RNA viruses Family includes common cold (rhinovirus) & polio viruses

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..Viral Hepatitis Hepatitis A (cont.) Transmission: Virus particles are present in the stool Fecal-oral route via contaminated food or water Saliva contact, sexual contact, and arthropods also have been implicated

..Viral Hepatitis Hepatitis A (cont.) Symptoms: Two to four week incubation period Nausea, vomiting, fever Abdominal pain Jaundice in many but not all cases Duration usually several weeks

…Viral Hepatitis Hepatitis A (cont.) Treatment & Prevention: Prolonged rest Hepatitis A Immune Globulin- (IG) contains antibodies that protect the body from hepatitis A. It's similar to the hepatitis A vaccine Hepatitis A vaccine

…Viral Hepatitis Hepatitis B: Also known as: Serum hepatitis Long-incubation hepatitis

…Viral Hepatitis Hepatitis B (cont.) Viral properties: Hepadnavirus family Nucleocapsid consists of DNA surrounded by hepatitis B core antigen (HBcAg)- HBcAg (core antigen) is a hepatitis B viral protein The core is surrounded by a lipoprotein envelope containing the hepatitis B surface antigen (HBsAg) The virus has also been called the Dane particle Large amounts of excess HBsAg are found in the serum & may be detected serologically

…Hepatitis B Hepatitis B infection occurs when liver cells become infected with the hepatitis B virus (HBV). Viral hepatitis is the leading cause of liver cancer and the most common reason for liver transplantation.

..Hepatitis B

..Viral Hepatitis Hepatitis B (cont.) Transmission: Contact with infected body fluids Blood, blood products, semen, vaginal secretions (urine, saliva also implicated).

…Viral Hepatitis Hepatitis B (cont.) Symptoms: Incubation period: four weeks - six months Nausea, fever Dark urine & clay-colored stools Abdominal tenderness Jaundice Duration of symptoms: months About 10% of patients remain carriers for several months

….Viral Hepatitis Hepatitis B (cont.) Treatment & prevention Hepatitis B Immune Globulin- Hepatitis B Immune Globulin- (IG) contains antibodies that protect the body from hepatitis B. Hepatitis B vaccination

….Viral Hepatitis Hepatitis C: Hepatitis C infects the liver. It can lead to permanent liver damage, liver cancer, and liver failure. Enveloped virus of the Flavivirus family Transmission & symptoms similar to B

..Viral Hepatitis Hepatitis D (Delta hepatitis): A small defective RNA virus that requires coinfection with Hepatitis B to replicate Co-transmitted with Hepatitis B Delta agent is a type of virus called hepatitis D that causes symptoms only in people who have a infection

….Viral Hepatitis Hepatitis E: small nonenveloped RNA virus of the calcivirus family Transmission & symptoms similar to Hepatitis A Just like all the other types of viral hepatitis, hepatitis E causes liver swelling and damge Hepatitis E transmission like there is for Hepatitis A

Human Immunodeficiency Virus (HIV) HIV (human immunodeficiency virus) is a virus that attacks the immune system ( the body’s natural defense system). Without a strong immune system, the body has trouble fighting off disease. Both the virus and the infection it causes are called HIV.

…Human Immunodeficiency Virus (HIV) Viral Properties A retrovirus An enveloped RNA virus that replicates through a DNA intermediate The DNA intermediate is synthesized by reverse transcriptase: an enzyme that makes a DNA molecule using an RNA template The DNA intermediate is spliced into host chromosomes, making the infection permanent

….Human Immunodeficiency Virus Transmission Contact with infected body fluids Blood, blood products, semen, vaginal secretions, breast milk Symptoms of HIV patients:Check images

….Human Immunodeficiency Virus What is the difference between HIV & AIDS? HIV: the Human Immunodeficiency Virus The cause of AIDS Also known as: HTLV-III and LAV Two known types: HIV-1 and HIV-2 AIDS: Acquired Immune Deficiency Syndrome Catastrophic immune system failure caused by HIV infection Symptoms & cases are usually defined by the CDC case surveillance definition

…..Human Immunodeficiency Virus Homework: 1.Check images of HIV & AIDS symptoms in patients 2. CDC Case Surveillance Definition for AIDS ? Category 1,2,3… Category A,B,C…

….Human Immunodeficiency Virus Symptoms & Secondary Infections Associated with AIDS: Acute Infection Fever, lymph node swelling, aches, fatigue, “flu-like” or “mono-like” symptoms Persistent Generalized Lymphadenopathy Lymph node swelling for greater than 6 months in two or more body areas (excluding the groin) Often an early manifestation that AIDS has developed

….Human Immunodeficiency Virus Symptoms & Secondary Infections Associated with AIDS (cont.): Constitutive Illness Weight loss, persistent fever, diarrhea Cancers Kaposi’s sarcoma (type of cancer) Certain lymphomas

Kaposi’s sarcoma Kaposi's sarcoma (KS) is a tumor caused by Human herpesvirus 8 (HHV8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV)

…Human Immunodeficiency Virus Symptoms & Secondary Infections Associated with AIDS (cont.): Bacterial Secondary Infections Mycobacterium Listeria Salmonella Mycoplasma Many others

….Human Immunodeficiency Virus Symptoms & Secondary Infections Associated with AIDS (cont.) Fungal Secondary Infections Candida and others Protozoan Secondary Infections Toxoplasma gondii Cryptosporidium Pneumocystis carinii

….Human Immunodeficiency Virus Symptoms & Secondary Infections Associated with AIDS (cont.): Viral Secondary Infections Herpes simplex Cytomegalovirus Many others Treatments Inhibitors of DNA replication Protease Inhibitors

E.Miscellaneous Viral Diseases Miscellaneous Pneumotrophic (viral diseases involving respiratory tract) such as influenza and common colds Viruses: Rhinovirus Adenovirus Respiratory Syncytial Virus-Respiratory syncytial virus (RSV), which causes infection of the lungs and breathing passages, is a major cause of respiratory illness in young children

….Miscellaneous Viral Diseases Miscellaneous Dermotrophic Viruses Measles (Rubeola) Rubella Mumps Fifth disease Papilloma (HPV)

..Miscellaneous Viral Diseases Miscellaneous Neurotrophic Viruses: Poliomyelitis Rabies Arbovirus Arenavirus (lymphocytic choriomeningitis) Others..several

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Bibliography Microbiology, A clinical Approach -Danielle Moszyk-Strelkauskas-Garland Science d d /home.html