Retroviridae I

Family Retroviridae

Diameter of virion 100 nm

Retroviridae: Capsids „mature“ outside the cell to

generate infectious virus particles

Formerly, Retroviridae were classified according to the morphologies of the mature capsids.

HIV-1 Aids

leukemias or sarcomas (cancer)

immunodeficiency

Shared Features of Retrovirus Particles:

1. Morphology: Retroviruses are generally spherical particles, approximately 100 nm in diameter, consisting of an internal protein core surrounded by an envelope of glycoproteins

2. Genetic Material: They contain RNA as their genetic material but produce a double-stranded DNA copy of their genome upon infection of a host cell

Features Distinguishing Retroviruses from Other Viruses:

1. Reverse Transcriptase: Retroviruses are distinguished from other viruses by the presence of reverse transcriptase, an enzyme that transcribes RNA into DNA

2. Genome Integration: They insert a DNA copy of their RNA genome into the DNA of a host cell, thus changing the genome of that cell

—> HIV Proteins: Gag, Pol and Env ORF encode multiple proteins Retroviruses

Simple Retroviruses:

1. Genome Organization: Simple retroviruses carry three virus-encoded genes (gag, pol, and env) and usually only this elementary information

2. mRNA Splicing: They have a simple pattern of mRNA splicing, typically making only one spliced mRNA

Complex Retroviruses:

1. Genome Organization: Complex retroviruses, such as lentiviruses and spumaviruses, contain extra non-structural genes, allowing them to encode and express additional proteins

2. mRNA Regulation: They exhibit a complex pattern of RNA regulation, leading to a greater variety of gene products

• Envelope proteins

  • Precurser, surfaceglyco, transmembrane glycp proteins

  • HIV Env glycoprotein trimer

  • (Gp120 + gp41) trimers form“ spikes“ in the virus envelope

• Group-specific Antigens (Gag)

  • Proteins are cleaved from the Gag polyprotein during maturation

• Enzymes

  
  

• Retroviridae: Accessory proteins

The HIV-1 replication cycle

• Retroviruses use 3 types of receptors for entry

• TM = trans Membrane domain

MLV: Endocytosis

HIV: Fusion of the viral membrane with the cellular membrane;

Endocytosis possible

• HIV variants enter different cells by using different co-receptors

Reverse transcription takes place in the viral capsid. This can occur in the cytoplasm or nucleus (e.g. macrophages)

in summary, retroviruses possess an RNA genome within their viral particles, but upon infection, this RNA is reverse transcribed into DNA, which becomes integrated into the host cell's genome. 

1. Reverse Transcription: Upon infecting a host cell, the retroviral RNA genome is reverse transcribed into a double-stranded DNA molecule by the enzyme reverse transcriptase

2. Integration into Host Genome: The newly synthesized DNA is then integrated into the DNA of the host cell, where it becomes a permanent part of the host's genome

3. Provirus Formation: The integrated DNA forms a provirus, which is transcribed and replicated along with the host cell's DNA

• Activation of HIV-1 expression by HIV-1 Tat and Rev

  during virus replication

• Tat = Trans-activator of transcription; RNA-binding protein

• The RNA structure bound by Tat (= TAR). TAR = Trans-activating response element

  Retroviruses

• The HIV-1 Rev protein: Regulator of expression of virion proteins

  • Rev binds to the RRE (Rev response element)

    in distinct HIV RNAs

  • Rev recruits host factors to HIV RNAs and facilitates

    expression of HIV virion proteins