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

RNA Viruses that Infect Humans

Introduction

RNA viruses are a diverse group of viruses that use ribonucleic acid (RNA) as their genetic material. Among these, retroviruses are notable for their unique replication strategy and their impact on human health, particularly through the Human Immunodeficiency Virus (HIV).

Characteristics of Human Retroviruses

Definition and Key Features

• Retrovirus: A type of RNA virus that uses reverse transcription to replicate within host cells.

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

• Integration: The newly synthesized viral DNA is permanently integrated into the host cell's genome, allowing for persistent infection.

• Example: Human Immunodeficiency Virus (HIV) is the most clinically significant human retrovirus and the causative agent of Acquired Immunodeficiency Syndrome (AIDS).

Structure of HIV

HIV is a complex retrovirus with several structural components that facilitate its infection and replication.

• 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 that encases the viral RNA.

• Viral RNA: The genetic material of HIV.

• Matrix: Layer beneath the envelope that provides structural support.

• Reverse Transcriptase and Integrase: Enzymes required for replication and integration of viral DNA into the host genome.

Host Cell Infection Mechanism

HIV can only infect host cells that express specific receptors and co-receptors.

• CD4 Receptor: Primary receptor found on helper T cells and some other immune cells.

• Co-receptors: CCR5 and CXCR4 are required for viral entry. CCR5 is found on white blood cells, while CXCR4 is present on CD4 cells.

• Attachment: HIV GP-120 binds to the CD4 receptor and a co-receptor, facilitating fusion and entry into the cell.

Epidemiology of HIV Infection

Transmission Routes

• Sexual Contact: The most common route, involving direct exchange of bodily fluids.

• Blood Products: Transmission through contaminated blood, sharing needles among drug abusers, and rarely through donated blood.

• Mother-to-Child: Babies can be infected before or during birth, or through breastfeeding.

• Environmental Stability: HIV does not survive long outside the human body.

Changing Face of HIV Morbidity

• Antiretroviral Therapy (ART): Since the 2000s, ART has slowed the progression of HIV disease and improved life expectancy.

• Demographics: HIV remains the most common cause of death among certain age groups, with approximately 130,000 new cases per year in the United States.

• Risk Factors: Multiple sexual partners, sharing needles, drug abuse, and mother-to-fetus transmission are major risk factors.

• Natural Resistance: Individuals with a mutated CCR5 co-receptor may have natural resistance to HIV infection.

Diagnosis of HIV Infection Among Adults and Adolescents

Diagnosis statistics are often categorized by transmission route and demographic group.

Transmission Category	Percentage of Diagnoses
Male-to-male sexual contact	Highest proportion
Heterosexual contact (male and female)	Significant proportion
Injection drug use (male and female)	Lower proportion
Male sexual contact and injection drug use	Lowest proportion
Other/Unknown	Minimal

Additional info: Exact percentages may vary by year and region; the table above summarizes the main transmission categories as described in the notes.

Multiplication Cycle of HIV

Overview of Replication Steps

The HIV multiplication cycle involves several key steps that allow the virus to infect host cells and produce new viral particles.

• Attachment: HIV binds to CD4 and co-receptors on the host cell surface.

• Fusion and Entry: The viral envelope fuses with the host cell membrane, allowing entry of the viral core.

• Reverse Transcription: Viral RNA is converted into double-stranded DNA by reverse transcriptase.

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

• Transcription and Translation: Host cell machinery transcribes and translates viral genes to produce viral proteins.

• Assembly: New viral particles are assembled at the cell membrane.

• Budding and Release: Mature virions bud from the host cell, acquiring an envelope from the host membrane.

Key Equation:

$\text{Viral RNA} \xrightarrow{\text{Reverse Transcriptase}} \text{Viral DNA} \xrightarrow{\text{Integrase}} \text{Integrated Viral DNA}$

Example: HIV Infection

HIV infection leads to progressive loss of CD4+ T cells, resulting in immunodeficiency and increased susceptibility to opportunistic infections.

Additional info: The multiplication cycle is a target for antiretroviral drugs, which inhibit various steps such as reverse transcription, integration, and viral protease activity.