Lecture 8 9

Retroviruses

• Retroviruses, like HIV, are characterized by their RNA genome, which is reverse transcribed into DNA before integration into the host cell's genome.
• HIV-1 is more prevalent than HIV-2, which is primarily found in West Africa.
• 5 million new HIV infections occur annually.
• HIV damages the immune system causing secondary infections and cancer. This is often referred to as Acquired Immunodeficiency Syndrome (AIDS).
• A person's CD4 cell count, typically between 500 and 1500 cells/mL, drops in HIV positive individuals, placing them at a higher risk of developing severe illnesses.

Retrovirus Structure

• Retroviruses have a core containing viral RNA.
• They also have proteins, lipids, and an envelope.
• A vital enzyme, reverse transcriptase, is crucial in the retroviral life cycle. Viral transcriptase plays a role in converting RNA into DNA.
• Viral integration into the host cell's DNA is a critical part of the lifecycle. After the genetic material of this virus has been transcribed into a complimentary DNA sequence, a new enzyme known as integrase is used to integrate this sequence into the host's genome.

HIV Transmission

• HIV is primarily transmitted through sexual contact (about 80%).
• Perinatal transmission (10%), involving transmission from mother to child during pregnancy, childbirth, or through breastfeeding, is significant.
• Blood and blood product transfusions (3-5%) can also transmit HIV.

HIV Pathogenesis

• Infected CD4+ T cells and macrophages migrate to lymph nodes, where high viral replication occurs.
• The initial infection is followed by a period of high viral load in the blood.
• This is often followed by a period of no apparent symptoms.
• Then, progressively, the CD4+ T cell count can decrease gradually.
• If the CD4+ cell count falls below 200/μL, this is often referred to as AIDS.

Undetectable = Untransmittable (U=U)

• Maintaining an undetectable viral load through consistent antiretroviral therapy (ART) prevents sexual transmission.
• Observational studies since 1996 show a clear link between reduced viral loads and reduced transmission risk.
• To ensure undetectable viral load, daily ART is essential.

Hepadnaviruses

• Hepadnaviruses, the group including hepatitis B virus (HBV), affect humans and some animals (including birds and mammals).
• Globally, over 400 million people are chronic carriers of HBV.
• HBV carries a partially closed double-stranded DNA genome, and replicates via an RNA intermediate.

HBV Infection

• Transmission occurs primarily through blood and semen (including sexual contact and drug abuse).

• Acute HBV infections are often mild to asymptomatic in children, but can progress to chronic infection in a proportion of adults.

• Chronic HBV infections result in over 500,000 deaths annually, often from complications like cirrhosis or liver cancer (hepatocellular carcinoma). Progression can occur in 15-40% of individuals with chronic infection.

• The incubation period is typically 2-3 months.

Hepatitis B in Malaysia

• Approximately 400,000 Malaysians live with chronic HBV, with a seroprevalence between 1.5-9.8%.
• Urban areas in Malaysia tend to have more undiagnosed cases than rural areas.
• Vertical transmission (from mother to child) is the primary method of transmission.
• Infants of HBsAg positive mothers must receive HBV immunoglobulin and vaccine within 12 hours of birth to reduce risk of transmission.

Non-Infectious HBV Particles

• These particles are produced by infected liver cells and released into the blood.
• They contain proteins that form the HBV surface, and they are used in some vaccines.
• Their shapes include spheres and filaments.

HBV Markers

• HBeAg: A soluble early antigen, present in acute HBV infections, but less common in chronic. Used for detecting acute HBV.
• HBsAg : Is crucial in diagnosing HBV infection, as it's a marker for surface antigen of the virus.
• Anti-HBc IgM/IgG antibodies: Represent an immune response to the core antigen. IgM antibodies are typically present during acute infection, while IgG antibodies indicate previous or chronic infection.
• Anti-HBs: Indicates immunity after infection or vaccination.

HBV Immunopathology

• HBV progeny bud out from hepatocytes, initiating a response.
• Cell-mediated immune responses, primarily CD8+ T cells, clear virus infections, but lead to liver damage during acute and chronic infections.
• Preventive measures include vaccination, safe practices, and avoiding drug/needle sharing.
• Treatment options like interferon-α (IFN-α) and nucleoside analogues may reduce viral load.

HBV Prevention

• Vaccination is available in two forms: stand-alone HBV vaccine and combined hexavalent vaccine (includes other childhood antigens).
• Vaccination can be administered to infants during the first few months of life, as well adults.
• This is a primary prevention method and is crucial in decreasing the incidence of chronic hepatitis B.