Immunosuppression increases JC polyomavirus large T antigen DNA load in the brains of patients without progressive

Julianne Bayliss1, Tanja Karasoulos, Catriona A McLean

  • 1Department of Medicine, Monash University, Seven, Alfred Centre, Alfred Hospital, Commercial Rd, Melbourne, VIC 3004, Australia. julianne.bayliss@monash.edu

Insights

Latent JC polyomavirus (JCV) brain infection is more prevalent in immunosuppressed individuals. Higher JCV DNA in kidneys correlates with higher brain JCV, suggesting a link to progressive multifocal leukoencephalopathy (PML) pathogenesis.

Area of Science:

  • Neurovirology
  • Immunology

Background:

  • The link between latent JC polyomavirus (JCV) infection and progressive multifocal leukoencephalopathy (PML) is not fully understood.
  • JCV is a common human polyomavirus, typically latent, but can cause severe neurological disease in immunocompromised individuals.

Purpose of the Study:

  • To investigate the prevalence and load of latent JCV DNA in brain and kidney tissues of patients without PML.
  • To explore the relationship between JCV DNA levels, immune status (HIV, CD4+ T-cell counts), and tissue location.

Main Methods:

  • Real-time quantitative polymerase chain reaction (qPCR) was used to detect and quantify JCV DNA.
  • Brain and kidney tissues from patients without PML were analyzed.
  • Statistical analyses, including correlation and comparison tests, were performed.

Main Results:

  • Immunosuppressed patients exhibited significantly higher JCV DNA levels in brain tissue compared to immunocompetent patients (P = .001).
  • In HIV-infected patients, lower CD4+ T-cell counts were inversely associated with brain JCV load (r(2) = -0.9; P = .01).
  • A strong positive correlation was found between JCV DNA loads in kidney and brain tissues (Spearman ρ = 0.65; P = .004).

Conclusions:

  • Latent JCV brain infection is significant in the context of immunosuppression.
  • Kidney JCV load may serve as an indicator for JCV presence in the brain.
  • These findings underscore the importance of latent JCV brain infection in the pathogenesis of PML.

Related Concept Videos

Cytomegalovirus Disease01:27

Cytomegalovirus Disease

Cytomegalovirus (CMV) disease is caused by human cytomegalovirus, a double-stranded DNA virus of the Herpesviridae family. While primary CMV infection is often asymptomatic in immunocompetent individuals, the virus can cause severe disease in neonates and immunocompromised patients. CMV is the most common cause of congenital viral infection in the United States, and a major pathogen in solid organ and hematopoietic stem cell transplant recipients.CMV is transmitted via bodily fluids, sexual...
Encephalitis ll: Pathophysiology01:26

Encephalitis ll: Pathophysiology

Encephalitis is inflammation of the brain parenchyma caused by direct viral invasion or immune-mediated mechanisms triggered by infections or tumors. Both processes lead to neuronal injury, disrupted neurotransmission, and diverse neurological symptoms, often with overlapping clinical and pathological features.Autoimmune EncephalitisIn autoimmune encephalitis, antibodies target neuronal antigens on cell surfaces, synapses, or within neurons. A key example is anti-NMDAR encephalitis, which can...
Immunodeficiency Diseases01:25

Immunodeficiency Diseases

Immunodeficiency disorders are conditions in which the immune system's ability to fight infectious disease and cancer is compromised or entirely absent. The immune system comprises a complex network of cells, tissues, and organs that work together to protect the body from potentially harmful invaders. When this system is deficient or not functioning properly, it leaves the body susceptible to infections, diseases, or other complications.
There are three main causes of immunodeficiency disorders...
Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Arboviral Encephalitis01:25

Arboviral Encephalitis

Arboviral encephalitis refers to brain inflammation caused by arthropod-borne viruses, particularly those transmitted through mosquito vectors. Among these, West Nile virus (WNV), a member of the Flaviviridae family, is a significant public health concern. WNV is an enveloped, positive-sense, single-stranded RNA virus. Human infection typically begins when an infected mosquito introduces the virus into the dermis during feeding. The primary transmission cycle involves birds as amplifying hosts...
Cytotoxic Edema: Pathophysiology01:21

Cytotoxic Edema: Pathophysiology

Cytotoxic edema is a form of cerebral edema characterized by intracellular swelling of neurons, astrocytes, and other glial cells. It develops when the mechanisms responsible for maintaining ionic gradients across the cell membrane become impaired. Under normal physiological conditions, the sodium–potassium ATPase actively transports sodium ions out of the cell and potassium ions into the cell, preserving osmotic balance and enabling electrical signaling. This pump requires a continuous supply...