15.2 Hepatitis, HIV, and Immunocompromised-Host Viruses

15.2 Hepatitis, HIV, and Immunocompromised-Host Viruses

Quick Answer: HAV is a fecal-oral picornavirus that causes acute hepatitis only. HBV (partially double-stranded DNA, blood and body fluids) and HCV (RNA, blood) can become chronic and are oncogenic. HIV is a retrovirus; diagnosis conceptually uses NAAT plus serology, and plasma viral load follows replication. In transplant and AIDS patients, watch CMV, HSV, EBV, BK virus (allograft nephropathy and hemorrhagic cystitis), and JC virus (PML). High-risk HPV types 16 and 18 drive most cervical cancers; screening NAAT is detailed in 15.3.

This section is about virus biology, transmission, chronicity, and pathogenicity. Antibody and antigen patterns for hepatitis, HIV, EBV, and CMV belong in the serology chapter. Direct-detection methods and HPV cervical screening belong in 15.3. Antiviral drug mechanisms and resistance are SM-only and are not M-tested.

Hepatitis A, B, and C

Hepatitis A virus (HAV) is a naked positive-sense RNA picornavirus. It is acquired by the fecal-oral route from contaminated food or water or from close contact in households and childcare. After an incubation of several weeks, it causes acute hepatitis: jaundice, dark urine, fever, and marked aminotransferase elevation. There is no chronic HAV infection and no carrier state. Outbreaks cluster around a common food source. Pathogenicity is largely immunopathology: the virus is not strongly cytopathic in hepatocytes; cytotoxic T-cell injury produces the hepatitis. Diagnosis is serologic (IgM anti-HAV) and is not a direct-detection problem in most laboratories.

Hepatitis B virus (HBV) is an enveloped, partially double-stranded DNA hepadnavirus. Transmission is parenteral, sexual, and perinatal—blood and body fluids, not feces. Adults who acquire HBV usually clear it; neonates and young children much more often become chronically infected. Persistence of covalently closed circular DNA in hepatocyte nuclei supports lifelong infection if immune control fails. Chronic hepatitis B produces cirrhosis and hepatocellular carcinoma through chronic inflammation and viral proteins such as HBx. HBsAg marks current infection; HBeAg correlates with higher infectivity; those patterns are serology. What M virology needs is the route, the DNA genome, the possibility of chronicity, and the oncogenic risk.

Hepatitis C virus (HCV) is an enveloped positive-sense RNA flavivirus transmitted primarily by blood (injection-drug use, unscreened transfusions historically, needlesticks). Sexual and perinatal transmission occur but are less efficient than for HBV. A large majority of untreated infections become chronic. The RNA-dependent RNA polymerase is error-prone, generating quasispecies that help the virus evade immunity; there is no HCV vaccine. Chronic HCV, like chronic HBV, leads to cirrhosis and hepatocellular carcinoma. Antibody screening is serology; NAAT detects HCV RNA and is used to confirm infection and to quantify viral load. Do not confuse fecal-oral HAV with blood-borne HBV/HCV on a transmission question.

HIV: biology and viral load

HIV-1 (and less commonly HIV-2) is a lentivirus in the family Retroviridae. The virion carries two copies of positive-sense RNA, reverse transcriptase, integrase, and protease. After entry, reverse transcriptase copies RNA into DNA; integrase inserts the provirus into the host genome. Envelope glycoproteins gp120 and gp41 mediate attachment and fusion. The primary receptor is CD4; co-receptors are CCR5 (R5 viruses, typical early infection) or CXCR4 (X4 viruses, more common later). Tropism for CD4-positive T lymphocytes, macrophages, and dendritic cells explains progressive cellular immunodeficiency.

Acute infection may produce a mononucleosis-like illness with high plasma viremia. A clinically latent period follows in which the provirus persists and CD4 counts slowly fall. AIDS is the late stage with opportunistic infection and certain malignancies. Pathogenicity combines cytopathic killing of infected CD4 cells, chronic immune activation, and loss of mucosal and cell-mediated immunity.

Plasma viral load is a quantitative NAAT (typically RT-PCR) that reports HIV RNA copies per milliliter. It is used to assess baseline replication, to monitor antiretroviral response, and to detect failure as a rising copy number. Diagnosis of HIV infection in routine adult screening is a fourth-generation antigen/antibody immunoassay with supplemental differentiation and NAAT as needed; those serologic algorithms are the serology chapter. This chapter’s job is to recognize HIV as an RNA retrovirus and to know that viral load is plasma NAAT, not DFA and not shell-vial culture. Whole blood or plasma collected in the tube specified by the assay (often EDTA) is the matrix; serum serology tubes are not interchangeable with VL plasma without the laboratory’s validation.

Immunocompromised-host viruses

Latency is the unifying pathogenic theme. Herpesviruses and polyomaviruses persist after primary infection and reactivate when T-cell surveillance drops—after solid-organ or hematopoietic transplantation, in advanced HIV, or during intensive immunosuppression.

CMV infects monocytes and endothelium, produces characteristic large cells with “owl-eye” nuclear inclusions, and is the most important viral pathogen of solid-organ and marrow transplant recipients. Disease includes pneumonitis, colitis, hepatitis, and, at very low CD4 counts, retinitis. Congenital CMV is the leading infectious cause of non-genetic sensorineural hearing loss. Laboratories monitor plasma CMV viral load by quantitative NAAT in transplant patients; histopathology and immunohistochemistry still identify tissue-invasive disease.

HSV in immunocompromised hosts is not limited to a few vesicles. It causes extensive mucocutaneous ulceration, esophagitis, pneumonitis, hepatitis, and encephalitis. Latency in sensory ganglia plus impaired CD8 control explains recurrences. Vesicle or ulcer swabs, plus CSF PCR when meningitis or encephalitis is in the differential, are the direct-detection specimens.

EBV infects B cells through CD21 and persists for life. In immunocompetent adolescents it causes infectious mononucleosis (serology chapter). In transplant recipients, uncontrolled B-cell proliferation produces post-transplant lymphoproliferative disorder (PTLD). In advanced HIV, EBV is linked to oral hairy leukoplakia and several lymphomas. Pathogenicity is oncogenic transformation of latently infected B cells when T-cell surveillance fails.

BK virus remains latent in the urogenital tract. After kidney transplantation it causes polyomavirus-associated nephropathy that can lose the allograft; after hematopoietic transplantation it causes hemorrhagic cystitis. Decoy cells in urine cytology are a clue; plasma and urine NAAT quantify replication. Do not assign this syndrome to JC virus.

JC virus is the polyomavirus of oligodendrocytes. Reactivation in the CNS produces progressive multifocal leukoencephalopathy (PML): multifocal demyelination without a mass-effect abscess. CSF JC virus NAAT supports the diagnosis. PML is an AIDS-defining illness and also occurs with certain monoclonal immunosuppressive therapies.

HPV mention and pathogenicity themes

Human papillomaviruses are naked dsDNA viruses with tropism for squamous epithelium. High-risk types, especially 16 and 18, drive most cervical cancers by expressing E6 and E7 oncoproteins that inactivate p53 and Rb. Low-risk types cause warts, not cancer. Cervical cancer screening with high-risk HPV NAAT plus cytology is section 15.3; here, remember that HPV is an oncogenic DNA virus of epithelium, not a hepatitis or retrovirus.

Across this section, pathogenicity patterns repeat: tropism (hepatocytes, CD4 cells, urothelium, oligodendrocytes), latency and reactivation (herpesviruses, polyomaviruses, HIV provirus), chronic inflammation and oncogenesis (HBV, HCV, HPV, EBV), and immune-mediated injury (HAV hepatitis). Those mechanisms, not drug names, are what M tests.