ROBBINS CH. 8 VIRAL INFECTIONS

Chronic Productive Infections

What type of infection involves the immune system being unable to eliminate the virus, leading to continued viral replication and persistent viremia?

Latent Infections

What are infections characterized by the persistence of viral genomes in cells that do not produce infectious virus/disease?

Acute (Transient) Infections

What are infections that elicit effective immune responses that eliminate the pathogens, limiting the duration of the infection?

Transforming Viral Infections

What are infections where viruses transform infected cells into benign or malignant tumor cells?

HSV-1, HSV-2, and VZV

What are the viruses belonging to the alpha-group of herpesviruses?

CMV, HHV-6, and HHV-7

What are the viruses belonging to the beta-group of herpesviruses?

EBV and KSHV/HHV-8

What are the viruses belonging to the gamma-group of herpesviruses?

Epithelial cells

What type of cells do alpha-group herpesviruses (HSV-1, HSV-2, VZV) infect?

Postmitotic neurons

What is the site of latent infection for alpha-group herpesviruses (HSV-1, HSV-2, VZV)?

A variety of cell types

What types of cells do beta-group herpesviruses (CMV, HHV-6, HHV-7) infect and produce latent infection in?

Lymphoid cells

What is the main site of latent infection for gamma-group herpesviruses (EBV and KSHV/HHV-8)?

Infectious Mononucleosis

What is the benign, self-limited lymphoproliferative disorder caused by Epstein-Barr Virus (EBV)?

Lymphomas and nasopharyngeal carcinoma

What are the human tumors associated with the pathogenesis of Epstein-Barr Virus (EBV)?

Fever, sore throat, generalized lymphadenopathy, and splenomegaly

What are the primary characteristics of Infectious Mononucleosis?

Atypical activated T lymphocytes (mononucleosis cells)

What cells appear in the blood, characteristic of Infectious Mononucleosis?

Antibody-mediated immunity

What immune response protects against measles virus reinfection?

Transient but profound immunosuppression

What is the effect of measles infection that results in secondary bacterial and viral infections, leading to morbidity and mortality?

Reduction in lymphocyte responses

What is indicated by the reduction in delayed-type hypersensitivity responses following measles infection?

Inhibition of the ability of infected dendritic cells to stimulate lymphocytes

What may be associated with the reduction in lymphocyte responses following measles infection?

RNA virus of the Paramyxoviridae family

What type of virus is the Measles virus?

Airborne route via aerosolized respiratory secretions

What is the transmission route for Measles virus?

SLAMF1 (Signaling lymphocytic activation molecule family member 1)

What is the initial receptor for measles virus infection, expressed on activated lymphocytes, dendritic cells, and monocytes?

Nectin-4

What cell-surface receptor for measles hemagglutinin protein is found on the basal surface of epithelial cells and is important for viral replication in the respiratory tract?

CD46

What cell-surface receptor was the first identified for measles virus, but is only used by culture-adapted virus (including the vaccine strain) and not wild-type virus?

Epithelial cells and leukocytes

What are the variety of cell types that Measles virus can replicate in?

Respiratory tract

What is the initial site where Measles virus multiplies?

Local lymphoid tissues

Where does Measles virus spread after multiplying in the respiratory tract?

Viremia

What process occurs after Measles virus replication in lymphatic tissue, leading to dissemination to many tissues?

T cell–mediated immunity

What host immune response helps control the measles viral infection and produces the measles rash in most children?

Croup, pneumonia, diarrhea, protein-losing enteropathy, keratitis, encephalitis, and hemorrhagic rashes

What severe diseases may measles virus cause in malnourished children with poor medical care?

Subacute sclerosing panencephalitis (SSPE)

What rare, late complication of measles is a persistent viral infection, potentially involving a replication-defective variant?

Measles inclusion body encephalitis (MIBE)

What rare complication of measles occurs in immunocompromised individuals?

Blotchy, reddish brown rash on the face, trunk, and proximal extremities

What is the appearance of the rash in measles virus infection, produced by dilated skin vessels, edema, and a mononuclear perivascular infiltrate?

Ulcerated mucosal lesions in the oral cavity near the opening of the Stensen ducts

What are Koplik spots, the pathognomonic sign of measles?

Necrosis, neutrophilic exudate, and neovascularization

What are the microscopic features that characterize Koplik spots?

Warthin-Finkeldey cells

What are the multinucleate giant cells with eosinophilic nuclear and cytoplasmic inclusion bodies that are pathognomonic of measles, found in lymphoid organs, lung, and sputum?

Mumps

What acute systemic viral infection is usually associated with pain and swelling of the salivary glands?

Paramyxoviridae family

What virus family does the Mumps virus belong to?

Hemagglutinin and neuraminidase

What are the activities of one of the two types of Mumps virus surface glycoproteins?

Cell fusion and cytolytic activities

What are the activities of the other type of Mumps virus surface glycoprotein?

Inhalation of or contact with respiratory droplets

What is the transmission route for Mumps virus entry into the upper respiratory tract?

Draining lymph nodes

Where does Mumps virus spread and replicate in lymphocytes after entering the upper respiratory tract?

Salivary gland ductal epithelial cells

What specific cells does the Mumps virus infect, resulting in desquamation, edema, and inflammation, leading to classic salivary gland pain and swelling?

CNS, testis, ovary, and pancreas

What other sites can the Mumps virus spread to?

Aseptic meningitis

What is the most common extrasalivary gland complication of mumps?

Bilateral in seventy percent of cases

What is the pattern of Mumps parotitis?

Edematous and diffusely infiltrated by macrophages, lymphocytes, and plasma cells

What is the microscopic appearance of the gland interstitium in Mumps parotitis?

Compress acini and ducts

What is the effect of macrophages, lymphocytes, and plasma cells infiltration in Mumps parotitis?

Swelling, edema, mononuclear cell infiltration, and focal hemorrhages

What microscopic features characterize Mumps orchitis?

Compromise the blood supply

What is the effect of parenchymal swelling in Mumps orchitis, due to the tight containment within the tunica albuginea?

Infection and damage of acinar cells

What event in the pancreas may release digestive enzymes, causing parenchymal and fat necrosis in Mumps pancreatitis?

Perivenous demyelination and perivascular mononuclear cuffing

What are the characteristics of Mumps encephalitis?

Poliovirus

What spherical, unencapsulated RNA virus causes acute systemic viral infection, leading to a wide range of manifestations from mild to paralysis?

Enterovirus genus

What genus does Poliovirus belong to?

Fecal-oral route

What is the transmission route for Poliovirus?

CD155 (epithelial adhesion molecule)

What molecule does Poliovirus bind to on human cells, expressed on epithelial cells, lymphocytes, and neurons?

Mucosa of the pharynx and gut (tonsils and Peyer patches in the ileum)

What are the initial sites where Poliovirus replicates?

Lymphatics to lymph nodes and eventually the blood

What is the pathway Poliovirus follows after replication in the pharynx and gut mucosa, producing transient viremia?

Motor neurons of the spinal cord (spinal poliomyelitis) or brainstem (bulbar poliomyelitis)

What specific cells does Poliovirus invade and replicate in within the CNS?

Antiviral antibodies

What immune molecules control Poliovirus disease in most cases, preventing containment failure in some individuals?

Blood or retrograde transport along axons of motor neurons

What are the routes of Poliovirus spread to the nervous system?

Mutation in the attenuated viruses to revert to wild-type, virulent forms

What causes rare cases of poliomyelitis that occur after vaccination?

West Nile Virus

What arbovirus of the flavivirus group causes acute systemic infection with a mild, self-limited presentation or neuroinvasive disease?

Mosquitoes

What is the vector that transmits West Nile virus?

Birds

What animals are the major reservoir for West Nile virus?

Skin dendritic cells

Where does West Nile virus replicate after inoculation by a mosquito?

Lymph nodes

Where does West Nile virus migrate to and replicate further before entering the bloodstream?

Blood-brain barrier

What anatomical structure can the West Nile virus cross in some individuals, allowing it to infect neurons in the CNS?

Immunosuppressed persons and older adults

What populations appear to be at the greatest risk for severe West Nile virus disease?

Meningitis, encephalitis, meningoencephalitis

What are the CNS complications of West Nile virus infection?

Hepatitis, myocarditis, and pancreatitis

What are the rare complications of West Nile virus infection?

Perivascular and leptomeningeal chronic inflammation, microglial nodules, and neuronophagia

What are the predominant morphological findings in the CNS of patients who died of West Nile virus infection?

Temporal lobes and brainstem

What brain regions are predominantly involved in the morphological findings of West Nile virus infection?

Flavivirus

What virus group does Dengue virus belong to?

Aedes mosquitoes

What is the vector for Dengue virus transmission?

Fever with headache, macular rash, and severe myalgias ("breakbone fever")

What are the clinical manifestations of non-severe Dengue?

Bleeding, liver failure, reduced consciousness, organ failure, plasma leakage, shock, and respiratory distress

What are the characteristics of severe dengue (dengue hemorrhagic fever)?

Hepatic necrosis and mononuclear infiltrates, septal thickening, and hyaline membrane formation in the lung

What are the features of widespread hemorrhages and severe pathology in severe dengue?

Cross-reactive antibody response

What type of immune response is stimulated by Dengue infection with one serotype that is weak and nonprotective for other serotypes?

Previous infection with a different serotype

What factor usually precedes the occurrence of severe dengue?

Antibody-dependent enhancement

What mechanism, involving cross-reactive antibodies and Fc receptors on macrophages, is thought to increase infectivity and contribute to severe dengue?

SARS-CoV-2 (COVID-19)

What novel coronavirus-mediated disease caused a worldwide pandemic first detected in Wuhan, China?

Bilateral ground-glass opacities

What are the common findings on chest imaging for severe COVID-19 illness?

Older individuals and those with comorbidities (diabetes, COPD, heart failure)

What populations are mainly affected by severe and sometimes fatal COVID-19 illness?

Diffuse alveolar damage (DAD) and inflammation with mainly mononuclear cells

What is the pathology revealed by histologic analysis of lung tissue in acute COVID-19 patients?

Herpesviruses

What are the large encapsulated viruses with double-stranded DNA genomes that most frequently establish latent infections in humans?

HSV-1 and HSV-2

What herpesviruses cause vesicular lesions of the epidermis at the site of entry and establish latent infection in sensory neurons?

Viral DNA remains within the nucleus of the neuron

What happens to the viral genome during HSV latency?

Latency-associated viral RNA transcripts (LATs)

What are the only viral RNA transcripts synthesized during HSV latency, with no viral proteins appearing to be produced?

Spread of virus from the neurons to the skin or to mucous membranes

What is the result of reactivation of latent HSV-1 and HSV-2?

Inhibit the class I MHC recognition pathway and produce decoy receptors that bind the Fc domain of immunoglobulin and inhibitors of complement

What are mechanisms used by HSVs to evade antiviral CTLs and humoral immune defenses?

Corneal blindness

What is HSV-1 a major infectious cause of in the United States?

Fatal sporadic encephalitis

What is HSV-1 a major cause of in the United States, usually involving the temporal lobes and orbital gyri of the frontal lobes?

Inherited mutations in TLR3 or components of its signaling pathway

What factor increases the risk of HSV encephalitis?

Disseminated herpesvirus infections

What complication may neonates and individuals with compromised cellular immunity suffer?

Increases the risk of HIV transmission fourfold and HIV acquisition twofold to threefold

What is the effect of HSV-2 infection due to ulceration and dampening of the immune response?

Large, pink to purple intranuclear inclusions (Cowdry type A)

What structures, consisting of viral replication proteins and virions, are contained within HSV-infected cells?

Fever blisters or cold sores

What are the HSV lesions that favor the facial skin around mucosal orifices (lips, nose), and are frequently bilateral?

Intraepithelial vesicles (blisters)

What are the lesions formed by intracellular edema and ballooning degeneration of epidermal cells in HSV infections?

Gingivostomatitis

What HSV-related condition, primarily caused by HSV-1, is usually encountered in children and is a vesicular eruption extending from the tongue to the retropharynx?