General characteristics of the Herpesviridae family
Herpesviruses are complex (enveloped) DNA viruses containing double-stranded linear DNA. The virion is oval-shaped, and the DNA is enclosed in an icosahedral capsid. Between the capsid and the lipoprotein envelope lies the tegument, which contains viral proteins and enzymes necessary to initiate replication. The envelope itself, bearing glycoprotein spikes, is formed from the inner layer of the host cell's nuclear membrane.
Genome features: in the herpes simplex virus and cytomegalovirus, the DNA consists of two fragments (short and long), each enclosed between two sets of inverted repeats. In Varicella zoster, the genome also consists of two fragments, but contains only a single inverted repeat.
Classification: three subfamilies
- Alphaherpesviruses include herpes simplex virus types 1 and 2, and the varicella-zoster virus (Varicella zoster). They are characterized by rapid growth, marked cytolytic effect, replication in epithelial cells, and the ability to enter a latent state in neurons.
- Betaherpesviruses include cytomegalovirus, and human herpesvirus types 6 and 7 (Roseolovirus, the causative agent of exanthema subitum in children). They are distinguished by slow reproduction and a tropism for secretory glands and kidneys.
- Gammaherpesviruses include the Epstein-Barr virus, the causative agent of infectious mononucleosis («kissing disease»), which exhibits lymphoproliferative activity.
Cytomegalovirus: taxonomy and cultivation
Family Herpesviridae, subfamily Betaherpesvirinae, genus Cytomegalovirus. A distinguishing feature is having the largest DNA genome among herpesviruses.
As an obligate intracellular parasite, it is cultivated only in living cells: fibroblast cultures and human embryonic lung diploid cells. A characteristic cytopathic effect is observed — the formation of giant cells (25–40 µm) with large intranuclear inclusions forming an «owl's eye» appearance.
Viral reproduction within the cell
- Attachment of the virion to host cell receptors and fusion of the lipoprotein envelope with the cell membrane.
- Penetration of the nucleocapsid into the cytoplasm and its transport to the nucleus; release of viral DNA inside the nucleus.
- Transcription using the host cell DNA-dependent RNA polymerase; export of mRNA into the cytoplasm.
- Translation on ribosomes with the sequential synthesis of early α-proteins (regulatory), β-proteins (matrix process enzymes, including viral DNA-dependent DNA polymerase), and late γ-proteins (structural — capsid and glycoproteins).
- Assembly of the nucleocapsid in the nucleus, budding through the nuclear membrane acquiring an envelope, and further modification in the Golgi apparatus.
- Exit from the cell via budding or lysis.
Epidemiology and pathogenesis
The source of infection is a sick person with an acute or latent form, frequently an asymptomatic carrier. Portals of entry: skin, mucous membranes, respiratory tract, placenta. Mechanisms of transmission are diverse: contact-household, respiratory, fecal-oral, transplacental, sexual, via blood transfusions, and organ transplantation. The virus is excreted in saliva, urine, semen, breast milk, and blood.
CMV establishes a lifelong latent infection with a tropism for salivary glands and renal tubules. Reactivation occurs during pregnancy, following blood transfusion, transplantation, and in immunodeficiencies. Humoral and cellular immunity are formed, but virus-neutralizing antibodies do not prevent the persistence of the virus in the body.
Clinical Forms
- Latent infection in the kidneys and salivary glands in immunocompetent individuals.
- In immunocompromised patients — pneumonia, vision and hearing impairments, cognitive disorders; oncogenic potential is also under discussion.
- Congenital cytomegalovirus infection — the most dangerous form: hepatosplenomegaly, jaundice, eye damage, cachexia, congenital myocarditis, malformations, and possible lethal outcome.
- Exacerbation of concomitant diseases, including Guillain-Barré syndrome with nerve root demyelination, paresis, and paralysis.
Laboratory diagnostics
Material for study: blood, urine, saliva, breast milk, cervical canal discharge, cerebrospinal fluid.
- Virological method — isolation in cell culture, optimally in shell vial tubes using immunofluorescent antibodies, which allows diagnosis within 72 hours. Enlarged cells and «owl's eye» inclusions are characteristic.
- Molecular genetic method — PCR for the detection of viral DNA.
- Serological methods — ELISA, CFT (complement fixation test), neutralization assay, IFAs with monoclonal antibodies.
Treatment and Prevention
Etiotropic therapy — nucleoside analogues: acyclovir, ganciclovir, which inhibit viral DNA polymerase. Interferons and their inducers, immunomodulators, and normal human immunoglobulin are used adjunctively. The scope of therapy is adjusted depending on the clinical form (pneumonia, myocarditis, congenital infection).
Specific prophylaxis is absent — a CMV vaccine has not been developed. Nonspecific prophylaxis includes compliance with sanitary and hygienic norms, rules of asepsis and antisepsis during medical manipulations, and limiting contact of immunocompromised individuals and pregnant women with infected persons, including children with congenital cytomegaly who are capable of shedding the virus into the environment for up to 5 years.
Key points
- Herpesviruses are complex DNA viruses with double-stranded linear DNA, an icosahedral capsid, and a tegument.
- The family is divided into three subfamilies: alpha-, beta-, and gammaherpesviruses.
- Cytomegalovirus belongs to betaherpesviruses and has the largest genome among family members.
- The cytopathic effect of CMV consists of giant cells with «owl's eye» inclusions.
- Reproduction includes the synthesis of early α- and β-proteins and late γ-proteins; assembly occurs in the nucleus, and the envelope is formed from the nuclear membrane.
- Congenital CMV infection with hepatosplenomegaly, jaundice, and developmental malformations poses the greatest danger.
- Diagnostics — PCR, ELISA, shell vial culture method with immunofluorescence.
- Etiotropic treatment — acyclovir and ganciclovir; no specific vaccine exists.