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Chapter 25: RNA Viruses that Infect Humans – Human Retroviruses and HIV

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RNA Viruses that Infect Humans

Introduction

This section covers the microbiology of RNA viruses that infect humans, focusing on human retroviruses, their structure, replication, and epidemiology. Retroviruses are a significant group of RNA viruses, with Human Immunodeficiency Virus (HIV) being the most clinically important example due to its role in causing Acquired Immunodeficiency Syndrome (AIDS).

Characteristics of Human Retroviruses

Definition and General Features

  • Retrovirus: A type of RNA virus that uses reverse transcriptase to convert its RNA genome into DNA, which is then integrated into the host cell's genome.

  • Reverse Transcriptase (RT): An enzyme unique to retroviruses that synthesizes double-stranded DNA from single-stranded RNA.

  • Integration: The viral DNA produced by RT is permanently incorporated into the host cell's DNA, allowing persistent infection.

  • Clinical Importance: HIV is the most notable human retrovirus, responsible for AIDS.

Example: HIV-1 and HIV-2 are the two main types of human retroviruses, with HIV-1 being the most widespread globally.

Structure of HIV

Viral Components

  • Envelope Glycoproteins: GP-120 (docking glycoprotein) and GP-41 (transmembrane glycoprotein) are essential for viral attachment and entry into host cells.

  • Lipid Membrane: Derived from the host cell membrane during viral budding.

  • Capsid: Protein shell enclosing the viral RNA.

  • Viral RNA: The genetic material of HIV.

  • Matrix: Layer between the envelope and capsid, providing structural support.

  • Reverse Transcriptase: Enzyme for RNA to DNA conversion.

  • Integrase: Enzyme that integrates viral DNA into host genome.

Example: The interaction of GP-120 with CD4 and co-receptors (CCR5 or CXCR4) is critical for HIV entry into host cells.

Host Cell Infection and Entry

Mechanism of Infection

  • HIV can only infect host cells expressing the CD4 receptor and a co-receptor (usually CCR5 or CXCR4).

  • CD4 receptors are primarily found on helper T cells and some other immune cells.

  • Co-receptors facilitate viral entry; individuals with certain CCR5 mutations may have natural resistance to HIV infection.

Example: The binding of HIV GP-120 to CD4 and CCR5/CXCR4 triggers fusion of the viral envelope with the host cell membrane, allowing viral entry.

Epidemiology of HIV Infection

Transmission Routes

  • HIV is transmitted by direct and specific routes:

    • Sexual intercourse

    • Transfer of blood or blood products

    • Mother to child (before or during birth, or via breastfeeding)

  • HIV does not survive long outside the human body.

Example: Needle sharing among drug abusers and unprotected sex with multiple partners are major risk factors for HIV transmission.

Changing Face of HIV Morbidity

  • Introduction of antiretroviral therapy in the 2000s slowed progression of HIV disease.

  • HIV remains the most common cause of death among people ages 25–44 in some regions.

  • Approximately 130,000 new cases per year in the United States.

  • Majority of new infections occur in males.

  • Natural resistance can occur due to genetic mutations in the CCR5 co-receptor.

Diagnosis of HIV Infection

Transmission Categories (2020 Data)

Diagnosis of HIV infection among adults and adolescents is categorized by transmission route. The following table summarizes the main transmission categories and their relative proportions:

Transmission Category

Percentage of Diagnoses

Male-to-male sexual contact

Highest proportion

Heterosexual contact (male and female)

Second highest

Injection drug use (male and female)

Lower proportion

Male sexual contact and injection drug use

Lowest proportion

Additional info: Exact percentages may vary by region and year; male-to-male sexual contact remains the leading transmission route in the United States.

Multiplication Cycle of HIV

Overview of Replication Steps

  • Attachment: HIV binds to CD4 and co-receptor on host cell.

  • Fusion and Entry: Viral envelope fuses with host membrane, releasing viral RNA.

  • Reverse Transcription: RT converts viral RNA into double-stranded DNA.

  • Integration: Viral DNA is integrated into host genome by integrase.

  • Transcription and Translation: Host machinery produces viral proteins and RNA.

  • Assembly: New viral particles are assembled.

  • Budding: Virions bud from host cell, acquiring envelope.

Example: The latency period of HIV infection is due to the integration of viral DNA into host genome, allowing the virus to persist undetected for years.

Key Formula

While there is no specific formula for HIV replication, the process of reverse transcription can be represented as:

Where ssRNA is single-stranded RNA and dsDNA is double-stranded DNA produced by reverse transcriptase.

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