Virology Fundamentals

• A virus is an infectious agent made of a genome (RNA or DNA) and a capsid protein.
• Many viruses have an envelope composed of a protein-containing lipid bilayer which distinguishes groups of viruses and complete virus particle combining these structural elements is called a virion.
• Virions function as delivery systems that protect the genomes and facilitate host cell binding and the payload includes the viral genome and enzymes needed for viral replication.
• The pathogenicity of a virus depends on structural and functional characteristics, and related viruses can produce distinct clinical pathologies.
• Viruses are divided into groups based on the type and structure of nucleic acid, the replication strategy, capsid symmetry, and the presence/absence of a lipid envelope.
• Differences within a virus family, including properties like host range, serologic reactions, amiino acid sequences of vital proteins, and nucleic acid homology, are the basis for genera division
• Viral species isolated from various geographic locations may have different nucleotide sequences and are referred to as strains.

The one-step growth curve and viral replication

• The one-step growth curve represents the change in the amount of infectious virus in a single cell infected by a single virus particle
• Data is obtained by following events in a large, synchronously infected cell population, with the experimental conditions manipulated to obtain synchronicity.
• The basic features of infectious cycles are consistent for all viruses, with time scale and progeny virus yield varying among virus families
• The one-step growth curve begins with the eclipse period, followed by exponential growth.

The eclipse period

• After the initial attachment of a virus to the host cell, its ability to infect other cells disappears which is called the eclipse period
• The eclipse period represents the time elapsed from the initial entry and disassembly of the parent viruses to the assembly of the first progeny virion.
• There is active synthesis of virus components during the eclipse period for most human viruses in a range of 1-20 hours

Exponential growth

• The number of progeny virus particles produced in the infected cell increases exponentially over some time, then reaches a plateau where no additional increase in virus yield occurs
• The maximum yield per cell is characteristic and reflects the balance between the rate at which virus is constructed, and the rate at which cells lose their ability to produce new virus particles
• The yield may range from 100 to 10,000 virions per cell for 8 - 72 hours or longer.

Steps in the replication cycle

• The replication process in sequence involves virus attachment to the host cell, leading to penetration and uncoating of the viral genome, which is then followed by gene expression and replication and ultimately ending in assembly and release of viral progeny.

Adsorption

• Adsorption occurs when there is initial attachment of a viral particle to a host cell that involves an interaction between specific molecular structures on the virion surface and receptor molecules in the host cell that recognize those vital structures
• Some viruses have specialized structures for attachment, like glycoprotein spikes found in viral envelopes(rhabdoviruses) while other viruses uses the unique folding of capsid proteins such as picornavirus
• Multiple copies of these molecular attachment structures are distributed around the surface of the virus, and in some cases, neutralizing viral infectivity occurs through antibody binding
• Receptors molecules on the host cell membrane are specific to each virus family
• Cellular membrane receptors for growth factors serve as receptors for particular viruses, these virus receptors are present only on specifically differentiated cells or each unique animal species.
• The presence or absence of host-cell receptors is an important determinant of tissue specification within a sustainable host species and also for the susceptibility/resistance of a species on a given virus.

Penetration

• Penetration occurs when the virion begins the passage from the surface of the host cell to across the membrane and into the cytoplasm
• Animal cells can be penetrated by viruses via receptor-mediated endocytosis as well as direct membrane fusion.
• Receptor-mediated endocytosis involves the cell internalizing compounds using serum lipoproteins and regulatory molecules, except the invading virus particles are bound to the host cell surface receptor in place of a normal ligament
• Cell membrane invaginates, enclosing the virion in/as an endocytic vesicle or endosome, the release of the version of the cytoplasm is either depending on one or more viral molecules or whether the virus is an enveloped membrane to which it then fuses (releasing the new capsid into the cytoplasm)
• Membrane fusion occurs with enveloped viruses entering a host cell by fusing their envelopes with the plasma membrane with one or more glycoproteins promoting this fusion
• During fusion, the new capsid is free inside the cytoplasm, where the vital membrane remains associated with the plasma

Uncoating

• Refers to the stepwise disassembly of the version that allows the expression of the viral genes that carry out the replication
• For enveloped viruses, the penetration process itself is the first form of uncoating and generally speaking most forms of an coding occur within the cell depend on enzymes, but complex viruses require newly synthesizes viral proteins for the process
• Loss of viral proteins during encoding leads to the loss of the virus particles' ability to infect creating an eclipse period, or viral genes beginning expression during the cycle

Genome replication for DNA and RNA viruses

• Each virus family differs in significant ways from all others in terms of macromolecular events composing the replication cycle, with the variation in viral genomes giving rise to great differences in the number of proteins the virus can code
• Smaller viral genomes depend on the host cell more for viral replication, small DNA viruses can produce 1-2 replication-related gene products, thus diverting cell process to those for viral replication, while larger DNA viruses provide virtually all enzymatic and regulatory molecules for a cycle
• Viral replication cycle in DNA starts with the 1st step of Transcription of early genes, then Replication of the virus which activates the proteins in translation, the Progeny of DNA activates assembly via nucleocapids

Genome replication for RNA viruses

• RNA must overcome the two following problems: the need to replicate the vital and how the viral particles produce numerous proteins in Eukaryotic host cells. First, there is no host cell RNA polymerase that synthesize viral complementary RNA, also the translations can only occur at a single intiation(single polypeptide) where viruses often need several including capsid proteins
• RNA overcomes this with four categories for replication:
  • I Viruses with a single-stranded genome (ssRNA) are (+) polarity that replicates via complementary RNA
    • Viral Replication, where the infecting original RNA-molecule acts as both a mRNA and a synthesyis for the complementary strand
    • Because origianl RNA is made of messenger polarity, it is translated after uncoating with celluar lysosomes with a protein cut by proteolytic processing by polymerase
    • ssRNA is template to synthesize viral RNA polymerase to synthesize complementary ssRNA (-), with progeny serving as a template for progeny (+)
  • II: (-) Polarity that replicates via complementary (+) strand
    • Viral Genomes here have two functions, protein synthesis, and templates for replication.
    • Complementary (+) strands are needed as intermediate due to (-) lack the ability to complete goals
    • The viruses are two-fold as (-) cannot be translated, thus viral RNA/polymerase is not synthesized immediately
  • III Viruses:
  • DNA RNA Genome:
    • Eukaryotic cells are unable to transcribe DNA genomes
    • The (-) strand is made of RNA Transcriptase (RNA polymerase depending from viral-code)
    • The virons consist of protein, and DNA.
    • RNA Trasncriptate are for both translation, and templates for (-) synthesis/ strands ending (+) formation. -IV: strand DNA/ replicated DNA intermediate.
    • Uses Polymerase( reverse transcriptase)
    • The viral uses viral integrase, the MRNA transcription ( host/ cell polymerase)

Assembly

• The nucleocapsids take place where the viral nuclei is (cytoplasm -RNA,nucleus DNA)
• DNA cells require nucleus synthesis/cytosol for assembly via self assemble for nuclei acid to connect with capids

Naked Viruses

• Completed at point of virion, disassembly of the cell is what causes distribution

Enveloped Virus

• Virus-specific glycoproteins - Cellular/host membrane causes the cell to have some version of viral/antigen specific
• Association with matrix protein and bonding with nucleocapaids/maturation for membrane
• Consequence: released continuously during replication(cell membrane looses integrity) and virus is proceeded
• most infectious are Extracelluar (membrane budding = internal cell such innerplasmic/nucleus
• If exposed to harsh damage lipids can be transferred by respiratory ways, where non enveloped have greater resilience

Viral infections and their effects on host

• Responses may varry such as having no effect( antigen specificity, latency cell alteration), or cell death
• Progeny, and infection are categorized using different methods:
  • A) Without - Abortive caused by cells lacking enzymes, promoter, replication. They lack permissiveness
  • B) Infaction without virus, genetic defects/replication problems, cell death
  • C) With - cell is antigenic and releases and allows infection of progeny, doesn't harm cell.
  • D) Latency - with no replication of the progen and in the future can release such virus, in cell chromosome.
    • Cells are turned into tumor and transformed
    • Increased efficieny for synthetic precursor/enzymes
    • Much of cells shut down, then the cell becomes lytic

Diseases with specific viral infections

• Chickenpox(Varicella) - highly contagious in skin disease primarly (2-7) year of age (4 million in US) via Herpesviridae family through repiratory routes (Varcia-zoster)

  • Attacment requires 6 types of glycoprotein that target respiratory/epithelial cells
  • Recognition results in homoral cellular immuntiy after (10-23) days, small vesicles are produced/rupture with scars (figure38.1) in 10 day/intesity
  • Vaccine (varivax) / Acylovir reduces illness
  • viral is still presnet though, existing via a domant DNA in cell ganglia/nerves.
  • immune compormised causes activation/painful vesicels/ replcaiton

• Influenza - respatory( flu) with orthromxy virus

  • A,B,C in groups of H & N antigens
  • The viruses are frequnency for the antigens for minor "drift" but major shift happens more
  • Antigen occurs yearly in A,B, and unverified in C
  • china has close pigs that can transfer the infection via human, pigs, back to pigs
    • recombination = antigenic
  • 1918, in 20 million cases: disaster - espanola
  • Asian, hong kong virus are still present via inhilation/digestion
  • in 1 to 2 incubtation = adherance
    • neruominidases for host and viral adhesion.
  • hem agglitium ( spikes), membrane of cells bulde ( receptos, via endocytosis
    • hydrophobic extrend to member after contact: RNA ncueocapsid release- cytosol
  • chills, ,fever, death by epithelical cells , 3 -7 days to subside
  • infections are very likely, by secondary
  • flutgen , virus is able to detect and take over a cell in (10-25) minutes
    • tamiflu /relenza attacks the enzyme, by blocking cell movement(aspirn)
    • inactive vacciens for chronics younger than 14 prevent disease
  • The strains for epidmnic influenza A are H2N and H3N2 hemagglutinin/neuromindase surface glycoproteins
  • A= 1-%or in winter
  • B = 3 % all flu cases in the US