8.1 Herpesviruses and their subfamilies
4 min read•august 1, 2024
Herpesviruses are a diverse family of DNA viruses that cause a range of human diseases. They're split into three subfamilies: Alpha, Beta, and Gamma, each with unique characteristics and infection patterns.
These viruses are masters of persistence, establishing lifelong latent infections in specific cell types. They can reactivate under certain conditions, causing recurrent symptoms and posing challenges for treatment and prevention.
Herpesvirus subfamilies and diseases
Classification and characteristics
Top images from around the web for Classification and characteristics
Viral Evolution, Morphology, and Classification | OpenStax Biology 2e View original
Is this image relevant?
Frontiers | Human NK Cells and Herpesviruses: Mechanisms of Recognition, Response and Adaptation View original
Is this image relevant?
Frontiers | Beta and Gamma Human Herpesviruses: Agonistic and Antagonistic Interactions with the ... View original
Is this image relevant?
Viral Evolution, Morphology, and Classification | OpenStax Biology 2e View original
Is this image relevant?
Frontiers | Human NK Cells and Herpesviruses: Mechanisms of Recognition, Response and Adaptation View original
Is this image relevant?
1 of 3
Top images from around the web for Classification and characteristics
Viral Evolution, Morphology, and Classification | OpenStax Biology 2e View original
Is this image relevant?
Frontiers | Human NK Cells and Herpesviruses: Mechanisms of Recognition, Response and Adaptation View original
Is this image relevant?
Frontiers | Beta and Gamma Human Herpesviruses: Agonistic and Antagonistic Interactions with the ... View original
Is this image relevant?
Viral Evolution, Morphology, and Classification | OpenStax Biology 2e View original
Is this image relevant?
Frontiers | Human NK Cells and Herpesviruses: Mechanisms of Recognition, Response and Adaptation View original
Is this image relevant?
1 of 3
- Herpesviridae family divides into three subfamilies: , , and
- Classification stems from biological properties including host range, replication cycle duration, cytopathology, and characteristics
- Herpesviruses exhibit varying degrees of host specificity
- Some infect a narrow range of hosts (HSV-1 primarily infects humans)
- Others have a broader host range (EBV can infect various primate species)
Alphaherpesvirinae
- Includes 1 and 2 (HSV-1, HSV-2) and (VZV)
- Associated diseases:
- HSV-1: oral herpes (cold sores)
- HSV-2:
- VZV: (primary infection) and (reactivation)
- Characterized by rapid replication cycle and establishment of latency in sensory ganglia
Betaherpesvirinae
- Comprises (CMV) and and 7 (HHV-6, HHV-7)
- Associated diseases:
- CMV: , in adults
- HHV-6: (sixth disease)
- HHV-7: roseola infantum, febrile illnesses in children
- Features slower replication cycle and establishment of latency in secretory glands, lymphoreticular cells, and kidneys
Gammaherpesvirinae
- Includes (EBV) and (KSHV)
- Associated diseases:
- EBV: , ,
- KSHV: , ,
- Characterized by tropism for lymphoid cells and establishment of latency in lymphoid tissues
Structure and replication of herpesviruses
Viral structure
- Enveloped, viruses with distinctive icosahedral capsid
- Tegument layer surrounds capsid, containing viral proteins important for initial stages of infection
- Viral genome ranges from 120-230 kbp, encoding 70-200 genes
- Variations exist among different herpesvirus species (HSV-1: ~152 kbp, EBV: ~172 kbp)
- Envelope contains viral glycoproteins crucial for attachment and entry into host cells
Replication cycle
- Attachment: viral glycoproteins bind to specific host cell receptors
- HSV-1 glycoprotein D binds to nectin-1 or HVEM receptors
- Entry: fusion of viral envelope with cell membrane or endocytosis
- Uncoating: nucleocapsid transported to nuclear pore, viral DNA released into nucleus
- Gene expression follows coordinated cascade:
- Immediate-early genes: transcriptional regulators
- Early genes: enzymes for DNA replication
- Late genes: structural proteins
- DNA replication occurs in nucleus using rolling circle mechanism
- Produces concatemeric DNA cleaved and packaged into capsids
- Assembly and egress:
- Nucleocapsids acquire tegument proteins
- Envelopment occurs by budding through nuclear membrane and cellular organelles
Latency and reactivation in herpesviruses
Latency mechanisms
- Viral genome exists as circular episome in nucleus of specific cell types
- Minimal gene expression during latency
- Latency-associated transcripts (LATs) crucial for:
- Maintaining latent state
- Protecting infected cells from apoptosis
- Epigenetic modifications regulate latent viral genomes:
- Histone modifications (acetylation, methylation)
- DNA methylation
Latency characteristics
- Different herpesvirus subfamilies establish latency in distinct cell types:
- Alphaherpesvirinae: neurons (HSV in trigeminal ganglia)
- Betaherpesvirinae: lymphocytes and monocytes (CMV in CD34+ hematopoietic progenitor cells)
- Gammaherpesvirinae: B lymphocytes (EBV in memory B cells)
- Latency programs vary among viruses:
- HSV: nearly complete transcriptional silencing
- EBV: multiple latency programs with varying gene expression profiles
Reactivation
- Triggered by various stimuli:
- Stress (physical or emotional)
- Immunosuppression (HIV infection, organ transplantation)
- Hormonal changes (menstruation, pregnancy)
- Molecular switch from latency to lytic replication involves:
- Expression of immediate-early genes
- Activation of transcriptional activators (HSV ICP0, EBV ZEBRA)
- Reactivation leads to resumption of lytic replication cycle
- Clinical manifestations may differ from primary infection (VZV reactivation causing shingles)
Epidemiology and transmission of herpesviruses
Global distribution and prevalence
- Herpesviruses ubiquitous pathogens with worldwide distribution
- Seroprevalence rates vary among geographic regions and socioeconomic groups
- Higher rates often observed in developing countries and lower socioeconomic populations
- HSV-1 seroprevalence: ~67% globally, higher in Africa (~87%)
- CMV seroprevalence: ~83% in developing countries, ~54% in developed countries
Transmission routes
- Close contact with infected bodily fluids primary mode of transmission
- Saliva (HSV-1, EBV)
- Genital secretions (HSV-2)
- Blood (CMV, KSHV)
- Vertical transmission from mother to child occurs for some herpesviruses
- CMV leading cause of congenital infections (~0.6% of live births in developed countries)
- Age of primary infection varies among different herpesviruses:
- Childhood: HHV-6 (peak incidence at 6-12 months)
- Adolescence/adulthood: EBV, HSV-2
Risk factors and special populations
- Coinfection with multiple herpesviruses common
- Can lead to more severe clinical manifestations
- May alter immune responses to individual viruses
- Immunocompromised individuals at higher risk for severe infections and reactivations:
- HIV/AIDS patients (increased risk of CMV retinitis, KSHV-associated malignancies)
- Transplant recipients (CMV reactivation leading to graft rejection)
- Occupational exposure risks for healthcare workers and childcare providers
- Increased risk of acquiring CMV infection
Key Terms to Review (37)
Acyclovir: Acyclovir is an antiviral medication primarily used to treat infections caused by certain types of viruses, especially herpesviruses, including herpes simplex virus and varicella-zoster virus. Its effectiveness in inhibiting viral replication makes it a crucial drug for managing herpesvirus infections and highlights its role within antiviral therapies.
Aerosol transmission: Aerosol transmission refers to the spread of infectious agents through tiny respiratory droplets that remain suspended in the air for extended periods. This mode of transmission is crucial in understanding how certain viruses, especially those that are airborne, can infect individuals over distances greater than what direct contact would allow. It highlights the importance of environmental factors, the nature of the viral particle, and the susceptibility of hosts in the context of viral spread.
Alphaherpesvirinae: Alphaherpesvirinae is a subfamily of the Herpesviridae family, known for its rapid replication cycle and ability to establish latency in host cells. This subfamily includes well-known viruses such as herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), and varicella-zoster virus (VZV). Members of this group are characterized by their neurotropic behavior, meaning they have a particular affinity for nerve cells, which is significant in understanding their pathogenicity and life cycle.
Antiviral therapy: Antiviral therapy refers to the use of medications specifically designed to treat viral infections by inhibiting the development and replication of viruses within the body. This approach is crucial for managing various viral diseases, particularly those caused by herpesviruses and papillomaviruses, as well as addressing both acute and chronic infections.
Betaherpesvirinae: Betaherpesvirinae is a subfamily of the Herpesviridae family, characterized by its members' ability to establish lifelong latency in the host. This subfamily includes notable viruses like cytomegalovirus (CMV) and human herpesvirus 6 (HHV-6), which are known for their slow replication rates and their impact on human health, particularly in immunocompromised individuals.
Burkitt's lymphoma: Burkitt's lymphoma is a type of non-Hodgkin lymphoma characterized by the rapid growth of tumors, primarily affecting the B cells of the immune system. It is often associated with infections from the Epstein-Barr virus (EBV), which belongs to the herpesvirus family, and is known for its strong link to immunosuppression and specific geographic locations, notably in Africa. Understanding this condition involves exploring its viral associations and its classification as an oncogenic disease.
Chickenpox: Chickenpox is a highly contagious viral infection caused by the varicella-zoster virus, leading to an itchy rash and flu-like symptoms. This infection primarily affects children but can occur in adults, especially those who have not been vaccinated or previously infected. Understanding chickenpox is essential for grasping the broader context of herpesviruses and their subfamilies, as it is a classic example of a disease caused by this group of viruses.
Congenital cmv infection: Congenital CMV infection occurs when the cytomegalovirus (CMV) is transmitted from a pregnant individual to their fetus during pregnancy. This infection is significant because it can lead to a variety of health issues for the newborn, including hearing loss, developmental delays, and other serious complications. Understanding congenital CMV infection is essential when examining the broader impacts of herpesviruses and recognizing the patterns of acute and chronic viral infections.
Cytomegalovirus: Cytomegalovirus (CMV) is a common virus belonging to the herpesvirus family, known for its ability to remain dormant in the body and reactivate later. It can be transmitted through bodily fluids and has significant implications for immunocompromised individuals, making it a crucial topic in understanding viral disease transmission and the characteristics of major virus families.
Direct contact: Direct contact refers to the immediate transfer of pathogens from an infected individual to a susceptible host through physical touch or bodily fluids. This mode of transmission is crucial in understanding how certain viruses spread, particularly in close-knit communities or among individuals who share physical interactions, influencing the dynamics of viral diseases.
Double-stranded DNA: Double-stranded DNA (dsDNA) is a molecular structure formed by two strands of nucleotides wound around each other in a double helix, making it the primary genetic material in many organisms, including most viruses. This configuration allows for stability and the precise replication and transcription processes necessary for genetic information storage and expression.
Endemic: Endemic refers to the constant presence and/or usual prevalence of a disease or infectious agent within a given geographic area or population group. In the context of herpesviruses, understanding endemic patterns helps in grasping how these viruses circulate in specific populations, their transmission dynamics, and their long-term impact on public health.
Enveloped virus: An enveloped virus is a type of virus that has a lipid membrane surrounding its protein coat, or capsid. This envelope is derived from the host cell's membrane as the virus buds off, and it plays a crucial role in the virus's ability to infect host cells. The envelope contains viral glycoproteins that are essential for attachment to and entry into host cells, making enveloped viruses generally more sensitive to environmental conditions than non-enveloped viruses.
Epidemic: An epidemic is a sudden increase in the number of cases of a disease above what is normally expected in a specific geographic area or population over a defined period. This term emphasizes the rapid spread and high incidence of infectious diseases, highlighting how certain viruses can affect both animal and human populations in various ways.
Epstein-Barr virus: Epstein-Barr virus (EBV) is a member of the herpesvirus family, known for its ability to establish lifelong infections in humans and its association with various diseases, including infectious mononucleosis and certain cancers. As a prominent member of the herpesviruses, EBV demonstrates unique characteristics that link it to cancer development, immune evasion, and its interactions with different organ systems.
Gammaherpesvirinae: Gammaherpesvirinae is a subfamily of herpesviruses known for their ability to establish latency in lymphoid tissues, leading to chronic infections. This subfamily primarily includes viruses that are associated with diseases in both humans and animals, highlighting their importance in virology and infectious diseases.
Genital herpes: Genital herpes is a sexually transmitted infection caused primarily by the herpes simplex virus type 2 (HSV-2) and, less frequently, by herpes simplex virus type 1 (HSV-1). It is characterized by painful sores in the genital area, and once contracted, the virus remains in the body for life, leading to recurrent outbreaks. This infection is significant as it is part of the larger family of herpesviruses, which includes various subfamilies that impact human health.
Herpes keratitis: Herpes keratitis is an eye infection caused by the herpes simplex virus (HSV), primarily affecting the cornea and potentially leading to vision impairment or blindness. This condition is a result of the reactivation of latent HSV that can occur in individuals who have previously been infected, emphasizing the virus's ability to persist in the body and cause recurrent issues.
Herpes labialis: Herpes labialis, commonly known as cold sores, is a viral infection caused primarily by the herpes simplex virus type 1 (HSV-1), although it can also be caused by type 2 (HSV-2). This condition is characterized by painful, fluid-filled blisters that typically appear on or around the lips and can recur due to the virus's ability to remain dormant in the body's nerve cells after initial infection. Understanding herpes labialis is essential in the context of herpesviruses and their subfamilies, as it exemplifies the clinical manifestations and transmission of this widespread group of viruses.
Herpes simplex virus: Herpes simplex virus (HSV) is a common virus that causes infections in humans, leading to oral and genital lesions. It exists in two main types, HSV-1 and HSV-2, each with distinct transmission routes and clinical manifestations, highlighting its relevance in understanding viral transmission, disease patterns, and host interactions.
Human herpesvirus 6: Human herpesvirus 6 (HHV-6) is a virus belonging to the Herpesviridae family, primarily associated with roseola, a common childhood illness characterized by high fever followed by a rash. This virus has two variants, HHV-6A and HHV-6B, which have distinct clinical manifestations and epidemiological profiles. Understanding this virus is crucial as it falls within the broader classification of herpesviruses, which are known for their ability to establish lifelong latent infections and potential reactivation under certain conditions.
Human herpesvirus 7: Human herpesvirus 7 (HHV-7) is a member of the Herpesviridae family, which primarily infects T-lymphocytes and is associated with several diseases in humans. It is closely related to human herpesvirus 6 and can cause various conditions such as roseola and other opportunistic infections, particularly in immunocompromised individuals.
Infectious mononucleosis: Infectious mononucleosis is a contagious illness primarily caused by the Epstein-Barr virus (EBV), a member of the herpesvirus family. Often referred to as 'mono,' this condition is characterized by symptoms such as fever, sore throat, swollen lymph nodes, and fatigue. Understanding infectious mononucleosis is important as it highlights the connection between herpesviruses and their ability to cause latent infections in humans, often reactivating later in life.
Kaposi's Sarcoma: Kaposi's Sarcoma is a type of cancer that forms in the lining of blood vessels and lymphatic vessels, often presenting as purplish spots or lesions on the skin. This cancer is closely associated with human herpesvirus 8 (HHV-8) and is commonly found in individuals with weakened immune systems, such as those with HIV/AIDS.
Kaposi's Sarcoma-Associated Herpesvirus: Kaposi's Sarcoma-Associated Herpesvirus (KSHV), also known as Human Herpesvirus 8 (HHV-8), is a member of the Herpesviridae family and is primarily linked to the development of Kaposi's sarcoma, a type of cancer. It belongs to the gammaherpesvirus subfamily and is associated with various other conditions, particularly in immunocompromised individuals such as those with HIV/AIDS, where it plays a significant role in oncogenesis.
Latency: Latency refers to a period during which a virus remains dormant within a host without causing any symptoms or detectable viral activity. This state allows the virus to evade the host's immune response and persist over time, often leading to recurrent infections. Understanding latency is essential for comprehending viral genetic elements, host interactions, the behavior of specific viral families, and strategies employed by viruses to avoid immune detection.
Mononucleosis-like syndrome: Mononucleosis-like syndrome refers to a collection of symptoms that resemble those of infectious mononucleosis, commonly caused by Epstein-Barr virus (EBV), a member of the herpesvirus family. This syndrome is characterized by fatigue, fever, sore throat, and lymphadenopathy, and can be caused by various viral infections beyond EBV, including cytomegalovirus (CMV) and certain herpesviruses. The association with herpesviruses highlights the diverse nature of viral infections and their impact on human health.
Multicentric castleman's disease: Multicentric Castleman's disease (MCD) is a rare lymphoproliferative disorder characterized by the abnormal growth of lymphoid tissue, leading to enlarged lymph nodes and systemic symptoms. This condition can be associated with human herpesvirus 8 (HHV-8) infection, particularly in individuals with compromised immune systems, such as those with HIV/AIDS. MCD presents with various clinical manifestations, making it important to understand its connection to viral infections and immune response mechanisms.
Nasopharyngeal carcinoma: Nasopharyngeal carcinoma is a type of cancer that arises in the nasopharynx, the area located behind the nose and above the back of the throat. It is strongly associated with certain viral infections, particularly Epstein-Barr virus (EBV), which is part of the herpesvirus family. This cancer is notable for its geographical distribution, being more prevalent in certain parts of Asia and North Africa, highlighting the role of environmental and genetic factors in its development.
Neonatal herpes: Neonatal herpes is a serious viral infection caused by the herpes simplex virus (HSV) that occurs in newborns, typically during delivery when the infant comes into contact with the virus in the birth canal. This condition can lead to severe complications, including neurological damage and even death if not promptly treated. Understanding neonatal herpes involves recognizing its transmission, clinical manifestations, and the importance of preventive measures for at-risk mothers.
PCR Testing: PCR testing, or Polymerase Chain Reaction testing, is a molecular biology technique used to amplify small segments of DNA, making it easier to analyze and detect the presence of specific genetic material. This method has become a cornerstone in diagnosing various viral infections, including herpesviruses and other clinically significant DNA viruses, as well as identifying oncogenic viruses associated with certain cancers.
Primary effusion lymphoma: Primary effusion lymphoma is a type of cancer that arises from B cells and is associated with infections caused by the Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8). This lymphoma typically presents as pleural or peritoneal effusions, meaning it often manifests in the form of excess fluid in body cavities rather than a mass or tumor. It is predominantly seen in immunocompromised individuals, particularly those with HIV/AIDS, linking it closely to herpesvirus pathogenesis and the immune response.
Roseola infantum: Roseola infantum, also known as sixth disease, is a common viral infection primarily affecting young children, characterized by a sudden high fever followed by a distinctive rash. This illness is caused by human herpesvirus 6 (HHV-6) and, less commonly, human herpesvirus 7 (HHV-7), which fall under the herpesvirus family and are significant in understanding the behavior and impact of clinically important DNA viruses.
Serology: Serology is the study of blood serum and its components, particularly focusing on the immune response to pathogens such as viruses. This field is crucial for diagnosing infections, determining immunity, and understanding disease progression. The insights gained from serological tests have historical significance in tracking viral outbreaks and are vital in categorizing various viral families, including herpesviruses, which are known for their complex interactions with the immune system.
Shingles: Shingles, also known as herpes zoster, is a viral infection caused by the varicella-zoster virus (VZV), which is a member of the herpesvirus family. This condition arises from the reactivation of the virus that remains dormant in nerve cells after an individual has recovered from chickenpox. Shingles is characterized by a painful rash that typically appears on one side of the body, often accompanied by other symptoms such as itching and tingling.
Varicella-zoster virus: Varicella-zoster virus (VZV) is a member of the herpesvirus family, specifically known for causing chickenpox (varicella) in children and shingles (herpes zoster) in adults. As a virus that establishes lifelong latency in the host's nervous system, it exemplifies the characteristic behaviors of herpesviruses, including reactivation and persistence, making it a critical subject in virology.
Viral shedding: Viral shedding is the process by which viruses are released from an infected host into the environment, allowing for potential transmission to other hosts. This release can occur through various bodily fluids such as saliva, blood, urine, and respiratory secretions, and is crucial for understanding how viruses spread and infect new individuals. The timing and amount of viral shedding can vary significantly between different viruses and also depend on the stage of infection.