Retroviridae Family and Subfamilies

Retroviridae

• Retroviridae is a family of enveloped viruses.
• Retroviruses have an ss(+) RNA genome with two identical copies.
• They have an icosahedral capsid (conical capsid for HIV).
• Retroviruses have a diameter of 80-120 nm.
• Retroviruses encode an enzyme called DNA polymerase-RNA dependent (reverse transcriptase).
• The DNA copy of the viral genome integrates into the host chromosome.

Retroviridae Subfamilies

• Oncovirinae: Associated with cancer and neurological disorders. Examples include mouse mammary tumor virus and Human T-cell lymphotropic virus (HTLV-1, HTLV-2, HTLV-5), Rous sarcoma virus (chickens), and Mason-Pfizer monkey virus.
• Lentivirinae: Have a nucleocapsid core with a cylindrical form. These cause diseases with a slow onset, including neurological disorders and immunosuppression. Examples include Human Immunodeficiency Virus (HIV-1, HIV-2), visna virus (sheep), caprine arthritis/encephalitis virus (goats).
• Spumavirinae: Cause no known disease, but they cause characteristic vacuolated "foamy" cytopathology. Examples include Human foamy virus and human retrovirus sequences that have integrated into human genomes like human placental viruses.

Human Immunodeficiency Virus (HIV)

• HIV is one of the most clinically relevant endemic diseases.
• HIV is caused by two lentiviruses, HIV-1 and HIV-2.
• HIV-1 is high in infectivity and virulence, higher heterosexual and vertical transmission, and has global prevalence.
• HIV-2 has low infectivity and virulence, and lower heterosexual and vertical transmission, and its prevalence is limited to West Africa.

HIV-1 Structure

• The Human Immunodeficiency Virus (HIV-1) is enveloped.
• Gag protein (group-specific antigen) forms the core and capsid proteins.
• Pol protein (polymerase) has reverse transcriptase, protease, and integrase.
• Env protein (envelope) has glycoproteins.
• Pro: protease
• Tat: transactivation of viral and cellular genes.
• Rev: regulation of RNA splicing and promotion of export to cytoplasm.
• HIV-1 has virulence-enhancing proteins.

HIV Viral Replication Cycle

• HIV binds to CD4 and chemokine receptors.
• HIV enters the cell by membrane fusion.
• Reverse transcription of viral RNA.
• Circular DNA forms.
• Viral DNA integrates into the host DNA.
• Transcription of viral DNA.
• Virion assembly.
• Budding and release.

HIV Receptors and Co-receptors

• CD4 is the primary receptor for HIV.
• CXCR4 and CCR5 are the co-receptors.
• HIV-1 primarily infects CD4+ T cells, macrophages, and cells of the myeloid lineage.

HIV Integration

• HIV viral DNA integrates into the host cell DNA, forming a provirus.

HIV Transmission

• HIV is transmitted through blood, semen, and vaginal secretions.
• Vertical transmission (mother to child) can occur through transplacental transmission, perinatal transmission, or breastfeeding.

HIV Disease Progression - Acute Infection

• Primary HIV infection involves the infection of cells in the blood or mucosa.
• Viral replication in regional lymph nodes causes widespread dissemination.
• Development of anti-viral responses and symptoms.
• Reduction in plasma viral load and resolution of acute infection.

HIV Disease Progression - Clinical Latency

• Few or no clinical manifestations for extended periods.
• Steady destruction of CD4+ T cells in lymphoid organs.
• Steady decline in circulating blood CD4+ T cells.

HIV Disease Progression - AIDS

• CD4+ cell count less than or equal to 200 per microliter.
• Catastrophic breakdown of host defenses with increased viremia and clinical disease.
• Common clinical features include opportunistic infections, neoplasia, and CNS involvement.

HIV Pathogenesis

• Acute HIV infection: Non-specific symptoms (flu-like), high viral load, collapse of CD4+ T cells.
• Host's immune response: Specific antibodies appear, but the immune response is not sterilizing.
• Clinical latency: Infection is active; virus persists in dendritic cells and macrophages; slow and steady decline of CD4+ T cells.
• Initial phase of the disease: Massive loss of CD4+ T cells; viral mutation allows evasion from host immune response.
• Advanced phase - AIDS: CD4+ count below 200 per cubic millimeter and increased viremia; opportunistic infections; HIV-related cancers, AIDS-related dementia; death within two years without treatment.

Long-Term Nonprogressors

• A small percentage of HIV-positive individuals do not progress to AIDS.
• Host genetics and viral factors are involved in disease progression in these individuals.
• Possible contributing factors may include: mutations in genes encoding cell-surface receptors or ligands, genes within human leukocyte antigens (HLA), cytokine or immune response genes.

AIDS - Clinical Signs

• Opportunistic infections (Pneumocystis carinii pneumonia, Cytomegalovirus infections, reactivation of herpes simplex virus, toxoplasmosis and esophageal candidiasis)
• Malignancies (lymphomas, Kaposi's sarcoma, HPV-associated cancers)
• Degenerative lesions of the CNS (AIDS-associated dementia)

HIV - Laboratory Diagnosis

• Serology tests (ELISA, rapid tests, Western blot) - detect antibodies.
• Molecular Tests (viral RNA/DNA detection) - detect viral load.
• HIV-1/2 antigen/antibody immunoassay for initial screening.
• HIV-1/HIV-2 antibody differentiation immunoassay to differentiate between HIV-1 and HIV-2.
• Real-time PCR for viral quantification in blood.
• p24 antigen assay to measure viral antigens in blood for early markers of infection.
• CD4+ T-cell counts and CD4/CD8 ratio are indicators of HIV progression.

Treatment for HIV Infection

• Highly Active Antiretroviral Therapy (HAART) is the current treatment for HIV.
• HAART involves a combination of antiviral drugs targeting different stages of the viral life cycle.
• These drugs target HIV fusion/entry, reverse transcriptase, integrase, and protein synthesis/assembly/protease.
• These drugs help improve health and prolong the life of HIV-infected individuals. There are no drugs able to fully eliminate the virus from the body.

Window Period

• The window period is the time between HIV acquisition and the detectability of the virus using laboratory tests.

Explore the fascinating world of Retroviridae, a family of enveloped viruses known for their unique ss(+) RNA genomes. This quiz covers the characteristics, diseases associated with its subfamilies, and the role of reverse transcriptase. Test your knowledge on Oncovirinae, Lentivirinae, and Spumavirinae.