Herpes and other DNA Infections

Herpes viruses and other DNA-based pathogens—like adenovirus, papillomavirus, and hepatitis B—cause chronic infections. These viruses integrate into host cells, triggering immune responses and clinical symptoms. Diagnosis and control are vital in nursing and microbiology.

Introduction

DNA viruses are a significant group of pathogens implicated in a wide variety of human diseases, ranging from mild self-limiting illnesses to severe, life-threatening conditions. Unlike RNA viruses, DNA viruses possess deoxyribonucleic acid as their genetic material, which enables them to exploit host cellular machinery for replication and persistence. The herpesvirus family, in particular, stands out due to its capacity for latency and recurrent infections.

Overview of DNA Viruses

Classification of DNA Viruses

DNA viruses are classified based on the structure of their genome (single-stranded or double-stranded), the presence or absence of an envelope, and their replication strategies. The major families of medically important DNA viruses include:

• Herpesviridae (e.g., herpes simplex virus, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus, human herpesviruses 6/7/8)
• Adenoviridae (e.g., adenovirus)
• Parvoviridae (e.g., parvovirus B19)
• Polyomaviridae (e.g., JC virus, BK virus)
• Poxviridae (e.g., variola virus, molluscum contagiosum virus)
• Hepadnaviridae (e.g., hepatitis B virus, though partially double-stranded)

Structure of DNA Viruses

DNA viruses can be enveloped or non-enveloped. Their genomes may be linear or circular, single- or double-stranded. The presence of an envelope generally increases susceptibility to environmental inactivation but assists in immune evasion. The capsid protects the viral genome and determines host cell specificity.

• Enveloped DNA viruses: Herpesviridae, Poxviridae, Hepadnaviridae
• Non-enveloped DNA viruses: Adenoviridae, Parvoviridae, Polyomaviridae

Replication Strategies

DNA viruses replicate within the host cell nucleus (except poxviruses, which replicate in the cytoplasm). Viral replication involves attachment, entry, uncoating, genome replication, assembly, and release. Latency and integration into the host genome are notable features for some DNA viruses, particularly herpesviruses.

The Herpesvirus Family

Types and Epidemiology

The Herpesviridae family consists of large, enveloped, double-stranded DNA viruses known for their ability to establish latency. There are eight human herpesviruses (HHVs), each associated with distinct diseases and epidemiological patterns:

1. Herpes Simplex Virus Type 1 (HSV-1): Primarily causes orolabial herpes; highly prevalent globally.
2. Herpes Simplex Virus Type 2 (HSV-2): Mainly causes genital herpes; sexually transmitted.
3. Varicella-Zoster Virus (VZV, HHV-3): Causes varicella (chickenpox) and herpes zoster (shingles); highly contagious.
4. Cytomegalovirus (CMV, HHV-5): Ubiquitous; causes asymptomatic infection in immunocompetent hosts but severe disease in immunocompromised individuals and neonates.
5. Epstein-Barr Virus (EBV, HHV-4): Associated with infectious mononucleosis and several malignancies.
6. Human Herpesvirus 6 (HHV-6): Causes roseola infantum; nearly universal infection by early childhood.
7. Human Herpesvirus 7 (HHV-7): Similar to HHV-6; less well characterised.
8. Human Herpesvirus 8 (HHV-8): Linked to Kaposi’s sarcoma, particularly in immunocompromised hosts.

Herpesviruses have a global distribution and are highly adapted to humans. Primary infection often occurs in childhood for many herpesviruses, with lifelong persistence due to latency.

Pathogenesis of Herpesviruses

Viral Entry and Spread

Herpesviruses typically enter the host through mucosal surfaces or broken skin. Initial replication occurs at the site of entry, followed by local spread and, for some viruses, dissemination via the bloodstream or neuronal pathways. For instance, HSV and VZV establish infection in epithelial cells and subsequently invade sensory nerve endings.

Latency and Reactivation

A hallmark of herpesvirus biology is latency—a state in which the viral genome persists in host cells with minimal gene expression and no production of infectious virions. The sites of latency vary:

• HSV-1/2 and VZV: Latency in sensory ganglia (e.g., trigeminal, sacral).
• CMV: Latency in monocytes and myeloid progenitor cells.
• EBV: Latency in B lymphocytes.
• HHV-6/7: Latency in T lymphocytes.
• HHV-8: Latency in B cells and endothelial cells.

Reactivation can occur due to immunosuppression, stress, or other triggers, leading to recurrent disease or asymptomatic viral shedding.

Immune Evasion Mechanisms

Herpesviruses have evolved multiple strategies to evade host immunity:

• Inhibition of antigen presentation (e.g., downregulation of MHC molecules)
• Modulation of cytokine responses
• Production of viral homologues of host proteins
• Latency-associated transcript expression to limit immune recognition

Clinical Manifestations of Herpesvirus Infections

Herpes Simplex Virus (HSV-1 and HSV-2)

• Orolabial Herpes (HSV-1): Presents as grouped vesicles on an erythematous base around the lips (cold sores). Primary infection may cause gingivostomatitis, especially in children.
• Genital Herpes (HSV-2 > HSV-1): Painful genital ulcers, dysuria, systemic symptoms (fever, malaise). Recurrent episodes are common.
• Complications: Herpetic whitlow (fingers), herpes simplex keratitis (eye), encephalitis (brain—often HSV-1), neonatal herpes (high mortality).

Varicella-Zoster Virus (VZV)

• Varicella (Chickenpox): Generalised itchy vesicular rash, fever, malaise. More severe in adults and immunocompromised individuals.
• Herpes Zoster (Shingles): Reactivation leads to painful, unilateral vesicular eruption in a dermatomal distribution, often preceded by neuropathic pain.
• Complications: Postherpetic neuralgia, secondary bacterial infection, encephalitis, disseminated disease in immunocompromised hosts.

Cytomegalovirus (CMV)

• Immunocompetent Hosts: Usually asymptomatic or mild mononucleosis-like illness.
• Immunocompromised Hosts: Severe systemic disease—pneumonitis, colitis, retinitis, encephalitis.
• Congenital CMV Infection: Leading cause of congenital infection; may cause sensorineural hearing loss, microcephaly, developmental delay.

Epstein-Barr Virus (EBV)

• Infectious Mononucleosis: Fever, pharyngitis, lymphadenopathy, splenomegaly, atypical lymphocytosis.
• Malignancies: Burkitt lymphoma, nasopharyngeal carcinoma, Hodgkin lymphoma, post-transplant lymphoproliferative disorders.

Human Herpesvirus 6 and 7 (HHV-6/7)

• Roseola Infantum (Exanthem Subitum): High fever followed by sudden appearance of a maculopapular rash as fever subsides; mainly affects infants and young children.
• Other Manifestations: Rarely, encephalitis or hepatitis.

Human Herpesvirus 8 (HHV-8)

• Kaposi’s Sarcoma: Vascular tumour presenting as purple-red plaques or nodules on the skin, especially in HIV/AIDS patients.
• Other Diseases: Primary effusion lymphoma, Castleman disease.

Laboratory Diagnosis of Herpesvirus Infections

Sample Collection

Appropriate specimen collection is critical and depends on the clinical presentation:

• Vesicular fluid or swabs for ulcerative lesions (HSV, VZV)
• Blood, urine, cerebrospinal fluid (CSF), tissue biopsies (CMV, EBV, HHV-6/7/8)

Microscopy

• Tzanck Smear: Rapid, but non-specific; multinucleated giant cells may be seen in HSV and VZV lesions.
• Histopathology: Intranuclear inclusions (Cowdry type A) in infected cells.

Viral Culture

• Gold standard for HSV and VZV detection, but slow (2–7 days) and less sensitive for latent or reactivated infections.

Serology

• Detection of IgM (acute) and IgG (past) antibodies; useful for EBV, CMV, VZV, and HSV epidemiological studies.
• Not always helpful in immunocompromised patients or in reactivation cases.

Molecular Methods (PCR)

• Highly sensitive and specific; detects viral DNA in clinical samples (blood, CSF, tissue).
• Essential for diagnosis of HSV encephalitis, CMV in transplant recipients, and quantification of viral load.

Antigen Detection

• Immunofluorescence assays and enzyme immunoassays can detect viral antigens in cells from clinical specimens; rapid and useful in some settings.

Other Important DNA Virus Infections

Adenovirus

• Pathogenesis: Infects epithelial cells; over 50 serotypes. Transmitted via respiratory droplets, faeco-oral route, or direct contact.
• Clinical Manifestations: Conjunctivitis, pharyngitis, pneumonia, gastroenteritis, haemorrhagic cystitis, myocarditis. Outbreaks in military and paediatric populations.
• Laboratory Diagnosis: PCR, viral culture, antigen detection, serology.

Parvovirus B19

• Pathogenesis: Targets erythroid progenitor cells in bone marrow; transmitted via respiratory secretions, blood products, or vertically.
• Clinical Manifestations: Erythema infectiosum (slapped cheek syndrome), arthropathy, aplastic crisis (in haemolytic anaemia), hydrops foetalis in pregnancy.
• Laboratory Diagnosis: PCR for viral DNA, serology for IgM/IgG antibodies.

Polyomaviruses (JC Virus, BK Virus)

• Pathogenesis: Establish latent infection in kidneys and lymphoid tissue; reactivation in immunosuppressed hosts.
• Clinical Manifestations: JC virus—progressive multifocal leukoencephalopathy (PML); BK virus—nephropathy and haemorrhagic cystitis in transplant patients.
• Laboratory Diagnosis: PCR (CSF for JC virus, urine for BK virus), serology less useful.

Poxviruses

• Variola Virus (Smallpox): Eradicated; caused severe febrile illness with characteristic pustular rash.
• Molluscum Contagiosum Virus: Causes benign, umbilicated skin papules, especially in children and immunocompromised individuals.
• Pathogenesis: Replicate in cytoplasm, evade immune responses via complex mechanisms.
• Laboratory Diagnosis: Electron microscopy (classic brick-shaped virions), PCR, histopathology.

Pathogenesis of Other DNA Viruses

The mechanisms of pathogenesis in non-herpes DNA viruses vary but often involve direct cytopathic effects, immune-mediated injury, and tissue tropism:

• Adenovirus: Lytic infection of mucosal epithelial cells; certain serotypes have oncogenic potential in animals.
• Parvovirus B19: Destruction of erythroid precursors leads to anaemia; immune complexes contribute to rash and arthropathy.
• Polyomaviruses: JC virus infects oligodendrocytes causing demyelination; BK virus damages renal tubular cells.
• Poxviruses: Large cytoplasmic factories for replication; immune modulation proteins facilitate evasion.

Clinical Manifestations

• Adenovirus: Respiratory infections (pharyngitis, pneumonia), conjunctivitis, gastroenteritis, haemorrhagic cystitis.
• Parvovirus B19: Erythema infectiosum (children), arthralgia/arthritis (adults), aplastic crisis (patients with haemolytic disorders), hydrops foetalis (foetus).
• Polyomaviruses: PML (JC virus) presents with progressive neurological deficits; BK virus nephropathy manifests as renal dysfunction in transplant recipients.
• Poxviruses: Molluscum contagiosum—flesh-coloured, dome-shaped papules; smallpox—fever, malaise, centrifugal pustular rash (historical).

Laboratory Diagnosis

• Adenovirus: PCR (respiratory, stool, urine samples), antigen detection, viral culture.
• Parvovirus B19: PCR (blood), serology (IgM/IgG); important in pregnant women and immunocompromised patients.
• Polyomaviruses: PCR (CSF, urine); viral load monitoring in transplant patients.
• Poxviruses: Electron microscopy, PCR, histopathological examination.

Major DNA Virus Infections

Recent Advances

Molecular Diagnostics

• Polymerase chain reaction (PCR) and real-time PCR have revolutionised the detection and quantification of viral DNA, allowing for rapid, sensitive, and specific diagnosis, especially in immunocompromised patients and for central nervous system infections.
• Next-generation sequencing (NGS) is emerging as a tool for detecting novel or drug-resistant variants.

Vaccines

• Varicella and herpes zoster vaccines (live attenuated and recombinant subunit) have significantly reduced disease burden.
• Smallpox vaccine played a pivotal role in eradicating variola virus.
• Research is ongoing for vaccines against CMV and other DNA viruses.

Antiviral Therapies

• Nucleoside analogues (e.g., acyclovir, valacyclovir, famciclovir) are effective against HSV and VZV.
• Ganciclovir, valganciclovir, and foscarnet are used for CMV infections, particularly in immunocompromised hosts.
• Emerging therapies target viral enzymes and immune modulation pathways.

Conclusion

Herpesviruses and other DNA viruses are significant causes of morbidity and mortality worldwide. Their ability to establish latency, evade the immune system, and cause a broad spectrum of diseases underscores the need for continued vigilance and research. Advances in molecular diagnostics, vaccination, and antiviral therapies have dramatically improved clinical outcomes, but challenges remain, particularly in immunocompromised populations and in the face of emerging viral resistance.

Future directions include the development of broader-spectrum antivirals, improved vaccines, and better strategies for monitoring and managing chronic infections. A comprehensive understanding of the pathogenesis, clinical spectrum, and laboratory diagnosis of DNA virus infections is essential for all healthcare professionals.

REFERENCES

1. Apurba S Sastry, Essential Applied Microbiology for Nurses including Infection Control and Safety, First Edition 2022, Jaypee Publishers, ISBN: 978-9354659386
2. Joanne Willey, Prescott’s Microbiology, 11th Edition, 2019, Innox Publishers, ASIN- B0FM8CVYL4.
3. Anju Dhir, Textbook of Applied Microbiology including Infection Control and Safety, 2nd Edition, December 2022, CBS Publishers and Distributors, ISBN: 978-9390619450
4. Gerard J. Tortora, Microbiology: An Introduction 13th Edition, 2019, Published by Pearson, ISBN: 978-0134688640 
5. Durrant RJ, Doig AK, Buxton RL, Fenn JP. Microbiology Education in Nursing Practice. J Microbiol Biol Educ. 2017 Sep 1;18(2):18.2.43. https://pmc.ncbi.nlm.nih.gov/articles/PMC5577971/

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