HHVs

Human herpesviruses (HHVs) are large double-stranded DNA viruses in the Herpesviridae family that infect humans. The eight commonly recognized HHVs are HHV-1 (herpes simplex virus type 1), HHV-2 (type 2), HHV-3 (varicella-zoster virus), HHV-4 (Epstein-Barr virus), HHV-5 (cytomegalovirus), HHV-6 (A and B), HHV-7, and HHV-8 (Kaposi sarcoma–associated herpesvirus). HHVs share an envelope, an icosahedral capsid, and a long replication cycle that enables lifelong latent infections with periodic reactivation. They are classified into Alpha-, Beta-, and Gammaherpesvirinae, differing in cell preference, latency sites, and reactivation patterns. Transmission occurs through close contact and fluids; latency allows persistence after recovery, with reactivation under stress, immunosuppression, or hormonal changes.

Clinical manifestations depend on the virus and host immunity. Primary infections range from asymptomatic to varicella (VZV), mono-like illness (EBV), or mucocutaneous lesions (HSV-1/2). Reactivation causes herpes labialis, genital herpes, shingles, CMV disease in the immunocompromised, or CMV retinitis. HHV-8 is linked to Kaposi sarcoma in immunosuppressed individuals, especially with advanced HIV. Vaccines exist for varicella and zoster; no licensed vaccines for HSV-1/2 or CMV. Antiviral drugs such as acyclovir, valacyclovir, and famciclovir treat many HHV infections; ganciclovir/valganciclovir are used for CMV. Resistance can occur.

Latency and diagnostics: after primary infection HHVs establish latent infections in specific cells (neurons or lymphoid cells) with intermittent reactivation. Diagnosis relies on PCR detection of viral DNA in blood or tissue, supported by serology for prior exposure; culture is used in some settings. Seroprevalence is high worldwide for most HHVs, with HSV-1, EBV, and CMV being particularly common. Public health considerations emphasize vaccination for VZV and management of recurrent disease.