3. Monitoring of viral infections

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Development Team

Paper Coordinator : Prof. Shibnath Majumder

Department of Zoology, University of Delhi Principal Investigator : Prof. Neeta Sehgal

Department of Zoology, University of Delhi

Content Writer : Dr M. R. Ngasainao, Dr Kiran Bala, Mr Raj Kumar

Deshbandhu College, University of Delhi

Content Reviewer : Prof. Sukhmahendra Singh

Banaras Hindu University Co-Principal Investigator : Prof. D.K. Singh

Department of Zoology, University of Delhi Paper : 10 Immunology

Module : 28 Immunity in Health and Diseases:

Immune Responses against viral Infections

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Description of Module Subject Name ZOOLOGY

Paper Name Zool 010: Immunology

Module Name/Title Immunity in Health and Diseases

Module ID M28: Immune Responses against Viral Infections

Keywords PRRs, Type Neutralizing antibodies, NK Cells, Dendrite Cell, Non like receptors, RIG-I like receptor, Toll like receptors Plasmacytoid Dendritic cell (pDC) Mitochondrial antiviral signaling NF-kB, Cyclophilin A, C-Type Lectins, TNF receptor, Inflammasomes Tetherin and Viperin, APOBEC RNAi, adaptive response, endogenous and exogenous antigen

1. Learning Outcomes

 The following module explains how viruses are handled by innate and adaptive immune system.

 The difference in type of immune response in innate and adaptive immunity.

 The mechanism involves in innate immunes and adaptive immune response against the viruses.

 The mechanism by which the viral evade both branches of immune system.

2. Introduction

In our day to day life process, we are exposed to large numbers of virus which has the capacity to infect and cause disease. Viral invasion usually occurs at mucosal surface lining the respiratory, gastro-intestinal and genitourinary tract. Primary infection can establish into disease in absence of adaptive immunity to viruses.

The response of immune system to virus is usually divided into innate immune response and adaptive immune response based on type of system activated. The innate immune response provides a generalized form of host response to various infectious agents. The innate immune mechanism acts to control the spread of infection and down regulate the viral replication. The recognition of virus or viral particles in innate immune response occurs via certain strategies based on pattern recognition receptors (PRRs). These receptors identify conserved microbial structure found throughout the same classes of microorganisms. Some metabolic products play crucial role as a part of PRRs and they are characteristics of particular microbial class.

In case of viruses, the various viral molecules are produce in the infected cell. However, the main targets for recognition by PRRs are viral nucleic acids. The innate immune system detects the viral RNA also. Viral nucleic acid is found in the endo-lysosome and cytoplasm of the host cell. On the other hand, host DNA is not found in these places. In cytoplasm, sensing mechanisms for both RNA and DNA of viruses are present. This sensing mechanism can

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example acute shortage of host protein synthesis, ER stress or change in activity of ion channels also serves as sensing mechanism. Once the virus is recognized by the innate immune system it leads to two step elimination method. First it leads to induction of antiviral response that is mostly mediated by type 1 interferon (IFNs). Second, it can cause activation of the adaptive immune response that would result in long lasting antiviral immunity and also antigen specific immunity. The priority of host response to viral infection is to eliminate the infected cells. The major response effector is the cell intrinsic mechanism based on Type 1 (IFN). However, this response can also be achieved in infected cell via cytotoxic lymphocyte, NK cells and CD8⁺ cells. Viruses are also prevented into host cells via neutralizing antibodies.

3. Monitoring of viral infections

In mammals, multiple mechanisms exist for identification of viruses. PRRs are one of the common mechanisms that are mostly utilized to detect the pattern associated with viral nucleic acid. Innate immune method of viral recognition includes both cell intrinsic and cell extrinsic based on type of cell involve infected or non-infected. Inside the cell sensing mechanism include NOD-like receptors (NLRs) and RIG-I-like receptors (RLRs). These receptors are generally activated in infected cells. TLR (Toll-like receptors) and c type lectins (CLR) transmembrane receptors are involved in cell extrinsic recognitions that are mediated by macrophage, dendritic cell and plasmacytoid dendritic cell (pDC). Fig. 1.

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Fig. 1: Various receptors involved in monitoring of viral infection.

Source:https://www.google.co.in/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0a hUKEwi_wcvVkY3RAhVKr48KHb1FAVoQjRwIBw&url=https%3A%2F%2Fwww.researchgate.net%2Ffigur e%2F236140057_fig2_Figure-2-Pattern-recognition-receptors-PRRs-recognize-wear-debris-around-

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3.1. Cell self-recognition of virus:

RNA viruses infecting a cell is recognized by melanoma differentiation- associated gene 5 (MDA 5), retinoic acid-inducible gene 1 (RIG 1) and cytoplasmic RNA helicases. The receptors belonging to RIG 1 like receptor are expressed in large number of cell type and recognize viral RNA helicase domains. RIG 1 also possesses a repressor domain at its C- terminus responsible for its inhibition and it also contains a catalytic domain to initiate antiviral signaling. Mitochondrial antiviral signaling (MAVS) protein is a membrane protein that acts as an adaptor for MDA5 and RIG 1 which are distributed on peroxisomes and mitochondrial membrane. (FADD) and caspases 8/10 are two protein kinases that act as target for MAVS (Fig. 2).

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Fig. 2: Intracellular mechanism of virus recognition.

Source:https://www.google.co.in/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0a hUKEwiMkMn9jI3RAhUIP48KHd9ZDacQjRwIBw&url=https%3A%2F%2Fwww.researchgate.net%2Ffigure

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3.2. Cytoplasmic viral DNA sensors:

There are multiple DNA sensing mechanism for DNA from various microorganism like bacteria, viruses, apoptotic host cells and synthetic B form DNAs example poly dA:dT B form of DNA triggers type 1 IFN through NK-kB and IRF3. DAI (commonly known as DLM 1 /ZBR1) is a molecule involve in intracellular DNA sensing (Fig. 3).

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Fig. 3: Intracellular viral DNA and RNA sensing mechanisms.

Source:https://www.google.co.in/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwjgk dDYjY3RAhVHuo8KHcNCAwQQjRwIBw&url=http%3A%2F%2Fjournal.frontiersin.org%2Farticle%2F10.3389%2Ffmic b.2016.00313%2Ffull&psig=AFQjCNG8-svcxySaew6jTU1hgKozlucdOQ&ust=1482678229606197

3.3. Cyclophilin A signature of viral infection:

In some cases, viral protein serves as signature of viral infection. Cyclophilin A is a peptidyl prolyl isomerase that calalyzes the cis/trans isomerization of x proline epitopes on target proteins. In dendritic cell, the innate response to HIV 1 depends upon the encounter of newly synthesized HIV 1 capsids and cyclophilin A present in cell leading to type 1 IFN response.

However, this capability of dendritic cell is lacking in CD4⁺ cells. Therefore, this mechanism is not utilized in human for type 1 IFN production because human DC are resistant HIV-1 infection. Cyclophilin A is incorporated into HIV 1 virion by binding it to capsid protein of HIV-1 to utilize it for its infectivity because viruses lacking this would be defective in the reverse transcription of viral RNA (Figure 4).

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Fig. 4: Cyclophilin A and its role in viral infection.

Source:https://www.google.co.in/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0a hUKEwiYr4TEjo3RAhXMPI8KHUZGDwIQjRwIBw&url=http%3A%2F%2Fwww.nature.com%2Fnm%2Fjou rnal%2Fv9%2Fn9%2Ffig_tab%2Fnm0903-1112_F1.html&psig=AFQjCNH7UO2p0Cotm2_yqSgHMMFG5 s0w_g&ust=1482678543296472

3.4. Virus recognition outside a cell:

3.4.1. Role of TLR:

Toll like receptors (TLR) are employed as pattern recognition receptor for majority of microorganism against the evolutionary conserved molecular pattern. The number of TLR present in a cell varies, in mice there are 11 functional TLR and in case of man there are 10 functional TLR. All TLR are basically type 1 transmembrane protein with an external domain that contains leucine rich repeat (LRR) that recognizes pathogen associated molecular pattern (PAMPs).

In a TLR, the transmembrane domain guides its localization and cytosolic domain contains the toll interleukin 1 receptor domain (TIR). This domain leads to activation of adaptor protein and produce pro-inflammatory cytokines and antiviral cytokines. Type 1 IFN production lead to activation of genes that suppress viral replication. TLR (1, 2, 3, 4, 5, 6, 11 and 12) are expressed on cell surface and TLR (3, 7, 8 and 9) expressed in endo-lysosomes.

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TLRs - in some viral invasion - are utilized as a passage for virus entry rather than to be acting as PAMPs receptor. Many viruses are recognized by TLR that are present in endosomal membrane (TLR 3, 7, 8 and 9) that comes in contact with the nucleic acid of viruses after their endocytosis in the form of viron (Fig. 5).

Fig. 5: Toll like receptors (TLRs) and its role in viral recognition.

Source:https://www.google.co.in/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwi7yf Clko3RAhUHNI8KHY8vDYsQjRwIBw&url=http%3A%2F%2Fjournal.frontiersin.org%2Farticle%2F10.3389%2Ffmicb.20 13.00276%2Ffull&psig=AFQjCNEHqco2DQEcd2qXUNXSODt3Jm8cIg&ust=1482679262401660

3.4.2. Role of C Type Lectins:

Plasma membrane in addition to TLR also contain another type of receptor that is capable of binding to viral antigen through their carbohydrate recognition domain and initiate Ca²⁺

dependent ligands binding. These receptors are C type Lecitin (CLR). There are various forms of CLR whose activity varies from each other for example some CLR do not bind to Ca²⁺ and some of them are used for inducing signal while others prefer to cause endocytosis of pathogens. CLR responsible for endocytosis include mannose receptor DEC 205 and langerin both of these are expressed in CD8⁺ DC and Langerhans cells, respectively. HIV viruses are cleared by binding to langerin molecules present on langerhans cells. Signal Inducing CLR includes DC SIGN and dectin 1. DC SIGN bind to Ebola virus and HIV1. DC

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SIGN does not cause activation of NFkB or cytokines production but modulates these activities through other PRR. Dectin1 is considered as receptor for fungal β – glucans. It leads to activation of NFkB (Fig. 6).

Fig. 6: Role of C – type Lectin in virus recognition.

Source:https://www.google.co.in/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0a hUKEwjpnPaWlY3RAhVKLo8KHeWGAEUQjRwIBw&url=https%3A%2F%2Fwww.researchgate.net%2Ffig ure%2F221754806_fig1_FIG-1-Major-pattern-recognition-receptors-PRRs-and-their-corresponding-Candida- PAMPs&psig=AFQjCNEzFMw7ZZc2upIxmEvuGb4b8LDkXA&ust=1482680083042884

4. Role of cytokines in antiviral response

4.1. Role of Tumor Necrosis Factor:

Tumor Necrosis Factor (TNF) receptors have cysteine rich extracellular binding domain. The binding of TNF to TNFR (TNF receptor) results in formation of a trimer. A death domain is present in the TNFR I cytoplasmic side that recruits an adaptor molecule called TRADD (Tumor necrosis factor receptor type-1 associated death domain protein). TRADD is responsible for the assembly of two separate signaling complexes receptor interacting protein

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(RIP I) or Fas associated protein with death domain (FADD) pro-caspases 8 and TRAF 2.

TRAF 2 activates JAK signaling pathway and RIP I activate NFkB.

4.2. Role of Type I IFN:

An appropriate immune reaction towards viruses in vertebrates requires the secretion of interferone type-I (IFN). IFN is responsible for inducing antiviral state in infected and uninfected cell lying in proximity. It also acts as a mediator of adaptor immune response. The other type of interferone type II and type III also act as potent antiviral cytokines.

4.3. Role of inflammatory Cytokines:

There are good numbers of cytokines that are involved in inflammatory responses that ultimately results in production of antiviral effectors molecules and simultaneously stimulates cellular recruitment and phagocytosis of infected cell. In addition, this also leads to adaptive immune response by activating cytotoxic T lymphocytes and neutralizing antibodies inflammatory cytokines IL-6, IL 1β and TNF that are secreted by infected DC and macrophages (Fig. 7). These cytokines are responsible for causing fever due to release of prostaglandin E2, acting on the hypothalamus that causes increase heat production from brown fat and vasoconstriction to prevent heat loss. Fever prevents the replication of viruses at higher temperature.

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Fig. 7: Mechanism depictin the production of the various type of interlukins through specific receptors mediated pathways and its role in defence mechanism.

Source:https://www.google.co.in/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0a hUKEwjVyrihlI3RAhVFMI8KHaGsCqUQjRwIBw&url=http%3A%2F%2Fsprout038.sprout.yale.edu%2Fimag efinder%2FFigure.external%3Fsp%3DSPMC3410142%252Fpjab-88-250-

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5. Role of Tetherin and Viperin

Tetherin undergoes high expression on stimulation by IFN (type I). It inhibits the release of retrovirus particle in the absence of viral protein unique (VPU). Tethrin binds the lipid and co-ordinates the change to inhibit the release or retrovirus particle. VPU uses the beta- TrCPE3 ubiquitin lipase complex and induce endosome trafficking, which is responsible for removing the tetherin from cell surface disabling it to restrict the release of enveloped virus.

Tetherin limits the release of retro-virus, filovirus. Viperin (Virus inhibitory protein - endoplasmic reticulum associated interferone inducible) is secreted in response to IFN and is responsible for inhibiting replication of viruses like HIV, dengue, alpha viruses, influenza

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virus and hepatitis virus. Viperin suppresses the activity of farnesyl diphosphate synthase and thus disrupt the release of influenza virus by dis organization of lipid rafts.

6. Role of APOBEC Family in innate immunity APOBEC

Apalipoprotein BmRNA-editing catalytic polypeptide (APOBEC) is a form of cytidine deaminases that have one to two catalytic deminase domains. The expression of APOBEC increases on stimulation of type 1 and type 2 IFN and has a constitutive expression in various cell types.

7. Role of RNA interference

One of the prominent anti-viral defense mechanism in some plants, fungi, insects and nematode is RNA interference (RNAi). RNAi operate in two steps, the first step result in identification of viral dsRNA by a molecule known as dicer endonuclease family that cleaves dsRNA into siRNA. Second step results in the incorporation of siRNA into RNA induced silencing complex (RISC). This complex guides the RNAase enzyme AGO (Agronaute protein) to a complementary sequence in viral RNA for its degradation and cleavage. There is no involvement of RNAi found in mammalian cells infected with virus. The mammalian cells also lack RdRPs and there is no amplification of siRNA, hence it shows a lack of systemic antiviral RNAi response. However, various other cell types are involved in antiviral response.

NK cell are responsible for detection and elimination of virus infected cells and also secrete IFN-γ that initiate other mechanism against virus. The cell surface of NK cells, possess two different classes of receptors, inhibitory and activating receptors. They initiate or inhibit the lysis of their target cell. The molecules responsible for inhibition of NK cells through inhibitory receptor are product of class 1 M.H.C that undergoes down regulation in situation of viral infection.

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8. Adaptive immunity to viral infection

Virus multiplies within the host cell by utilizing its biosynthetic machinery thereby enable to infect new cells within host body. In acute infection, there is a competition between the virus replication and survival of the host cell. That either the virus multiply and lead to host death or it can lead to virus clearance chronic infection that can allow virus to replicate up to weeks, months and year in host. This overall event lead to immune suppression and persistence of virus in host humans acting as a ecological baggage for the viruses.

Some viruses have co-evolved with humans for example Herpes Simplex Virus (HSV) and Epstein Barr Virus (EBV) which have developed latency to suppress the host defense and sustained in human population. There are large numbers of other viruses that have devised mechanism to maintain themselves at low level in infected individuals and continue themselves by infecting previously unexposed individuals. These individuals develop either mild or severe form of disease and act as reservoir of infection. Some animal viruses are capable of jumping from their natural host to human and are responsible for major pandemic causing zoonotic diseases in human. For example, HIV causes AIDS, SARS coronavirus causing severe acute respiratory syndrome and HINI influenza A virus causing swine flu. In most cases, viral infection leads to tissue or organ damage but some viruses are oncogenic, capable of inducing cancer for example human herpes virus 8, hepatitis B virus, hepatitis C virus and human papilloma virus.

8.1. In sight to adaptive immunity to virus infection:

Adaptive system takes few days to learn about the type of virus infection and it employs the B and T lymphocyte to recognize the viral constituents. They bind to the viral constituents through their B cell receptor and T cell receptor that are expressed by a limited number of cells against a particular virus. Thus, they are responsible in establishing immunological memory.

8.2. B cell response to viral antigens:

B cell can identify both the soluble and membrane bound viral antigens. In case of viral infection most of the antigens are actually presented by antigen presenting cells (APC) after

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antigen processing and presentation. B cell binding to viral antigen results in either B cell activation or proliferation. It also leads to internalization of viral antigen via B cell receptor and result in cleavage of viral antigen by endocytic pathway. This will present the antigenic peptide bounded to M.H.C II molecule on B cell surface and its recognition by viral specific T cell receptors (TCR) present on CD4⁺ cell (T helper cell), known as TFH or T follicullar helper cells. This can lead to secretion of cytokines by T helper cell and proliferation of B cell. B cell activation can also take place without involvement of T cell. These viral antigens are called T-independent antigens. B cell receptors (BCR) can lead to signal transduction only when there is clustering of 1gM molecules bind to antigen 1gM is associated two other membrane spanning molecule 1gα and 1gβ having an immune-receptor tyrosine activation motif at their cytoplasmic domains. BCR clustering results in phosphorylation of tyrosine and further signaling of B cell binds to the virion via their antibodies. The entire virion is internalized and the degraded peptides formed after cleavage is displayed on the B cell surface through M.H.C II molecule. This antigenic peptide is then presented to T helper cell followed by adhesion of B cell to T cell. Receptor CD 40 present on B cell and CD 40 ligand on TFH cells undergoes CD 40 and CD 40 ligand interaction. This process helps in the proliferation of B cell via virial co-stimulatory receptor and cytokines out of this cell to cell interaction.

The interaction between specific T cell and B cell leads to two pathways: In first step, proliferation of B cells occurs followed by its differentiation into plasma cell. Plasma cell formed secretes large amount of soluble antibodies to target antigen on virion. The plasma cell then undergoes class switch from IgM to IgG, IgE or IgA and survive for few days.

These antibodies producing plasma cells in germinal center undergo affinity maturation for greater strength of binding. In germinal center B cell divides after every 6 to 8 Hours.

8.3. Recognition of viral antigen by T cells:

T cells uses T cell receptors (TCR) to respond to viral antigen. This T cell receptor employ α, β chain heterodimer to bind to viral antigens. Some TCR also have γ, δ chain, but such receptors are not actively involved in antiviral response. In T cell immune response, the

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products of viruses are important for recognition. The exogenous antigens are degraded and present along with M.H.C II molecule through the endocytic pathway. Endogenous viral antigens are viral proteins translated form virus RNA by utilizing the host metabolic machinery. These viral proteins are first ubiquitinized and degraded by proteasomal complex through cytosolic pathway and are presented to CD8⁺ cells by M.H.C.I molecule. Humoral antibodies bind to the viral antigens present on viral surface and neutralize them.

Alternatively, they determine the antigen present on viral surface and prevent the binding of the virus to the host cells.

8.4. Viral antigen and its neutralization by antibodies:

Immunoglobulin (Ig) secreted by plasma inhibits the binding of virus to host cell and prevents infection and re-infection. The antibodies like IgG, IgA and IgM prevent the viral envelope fusion with host cell. Some classes of antibodies, promotes phagocytosis of viral particles. IgG and IgM can cause complement activation and opsonization by C3b followed by lysis of viral envelope.

8.5. B cells and primary viral infection:

Some viral infections caused by polyoma virus, vesicular stomatitis irus and rota-virus is controlled only by B cell in the absence of T helper cells. This is only possible due to repetition of viral antigen on their surface that enables the IgM antibodies to neutralize them in the absence of T helper cells. Therefore, a high level of IgM antibodies and low level of IgA and IgG shows a better result in viral suppression in acute phase of viral infection. Fla virus infection shows that only antibodies are sufficient in controlling the infection but on prolong infection T cell response is often consider good for elimination of viral infection.

Both B and T cell are important for protection against influenza virus both CD₈⁺ and CD₄⁺. In the absence B cell and T cell immune system fails to mount an appropriate response to viral infection.

8.6. B cell and secondary viral infection:

A preformed antibody possesses better protection properties against number of viruses.

Preformed antibodies from mother to a fetus via blood protect the new born from hepatitis B,

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rubella polio virus, herpes virus influenza virus and respiratory syncytial virus. These antibodies are very much potent and are capable to protect the new born from viral infection that can only be controlled by CTL in case of primary infections.

9. How virus evade immune system.

9.1. Change in antigen displayed on surface:

Some viruses evade recognition from the immune system by changing the antigen displayed on a constant basis. For example, influenza viruses change their surface antigen that results in forming of a new strain. Due to change in the strain type repeated infection occurs. HIV shows a higher degree of variation in their antigen than influenza virus due to faster rate of mutation.

9.2. Ability of complement inhibition:

Binding of viruses to antibodies results in the formation of antigen-antibody complex. This complex can lead to lysis of the viruses only when complement proteins are present followed by their elimination through phagocytosis. Viruses have developed mechanism to escape from these complements mediated destruction. Vaccinia virus produce a complement control protein called Vaccinia Complement Control Protein (VCP) that promotes cleavage of C3b and C4b by factor I, thus, blocking the classical pathway of complement activation.

9.3. Cytokine inhibiting proteins:

A large number of viruses are capable of producing protein that evades the host specific and non-specific defense mechanism. Viral infection in many cells leads to production of cytokines like IFN α and β. IFN α and β are responsible for production of antiviral protein in nearby cell. This antiviral protein is known as virus associated RNAs I (VAI). Adenovirus and Epstein Baa virus overcome this antiviral action of VAI by inhibiting the action of DNA dependent activator of IRFs (DAI).

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9.4. Degradation of proteins:

Antigenic protein is presented on the cell surface following degradation by proteolysis in cases of cells infected with Epstein Barr Virus (EBV). EBV encodes a viral protein, EBNA I, that contains glycine-alanine repeats that interferes with proteasomal complex. In case of Human Cytomegalo Virus (HCMV), the infected cells produce a viral protein phospho- protein 65 (pp65) that inhibits antigenic peptide production for T cell receptor.

9.5. MHC class I down regulation:

Role of class I MHC is to present antigenic peptide to CD8⁺ cell that are known as cytotoxic T-lymphocyte (CTL) and plays a crucial role in virus infected cells elimination. There are viruses that cause attenuation in class I MHC expression and thus inhibit its presentation on cell surface. This allows the virus infected cell to escape from CTL action by down- regulating cytosolic pathway proteins like TAP and LMPs.

9.6. MHC class I molecule retention in cell:

MHC class I can be retained inside the endoplasmic reticulum (ER) or moved out of ER. On reaching the cell surface the structure of MHC class I can be modified by viral proteins.

10. Summary

Viruses invade human cells to cause primary infection which can be established to disease.

Immune system protects the body from such diseases. Human cell tackles the invading virus through innate and adaptive immune response. The first step of the immune response is detecting viruses or viral particles or both. In mammals, there exist multiple mechanisms for doing so. This mechanism can be intrinsic or extrinsic. In both the case, pattern recognition receptors (PRRs) are deployed. PRRs are receptors that identify conserved microbial structure found throughout the same classes of microorganisms.

Cells, therefore monitors the presence of viral particles (DNA, RNA and viral proteins). The two-important class of PRRs recognizes the viral particles and activates the downstream Immune responses are Toll like receptors (TLRs) and type-C lecithin receptors (CLRs). The Recognition of virus or viral particles leads to induction of Antiviral response mediated by

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type-1 interferons (IFNs) and activation of adaptive immune response. TLRs activation leads to production of pro-inflammatory and antiviral cytokines, while TLRs activation leads to activation of NFkB and endocytosis of virus/ viral particles. Certain molecules are also activated that performs important roles in immunity against viral infection. These molecules include viperin which are lipid raft associated proteins that limits the release of viral particles and theterin which are endoplamic reticulum interferone associated proteins that disturbs the lipid raft of virus. RNA interference or iRNA also plays a curcial role in detecting viral dsRNA and cleaving it to small interference RNA (siRNA) with the help of dicer endonucleases. These siRNA are incorporated in RNA induced silencing complex which are then degraded by RNAase enzyme Argonuate protein (AGO).

Epitope binding of viral particles with antibody in our body activates certain types of white blood cells. B cell proliferates to produce plasma cells which produces antibody and memory cells which serves for long term immunity. Depending on integration of viral genome in the infected cell two pathways are deployed. Cytosolic pathway when there is no integration of viral genome and the later endocytotic pathway. In both case, processing of viral genome occurs to display MHC II and MHC I molecules respectively to mark the cell for destruction or elimination to prevent further spread of infection.

Though the immune system displays variety of mechanism to tackle viral infection, viruses do evade the immune system. They do so by either changing the antigen displayed on the cell surface, inhibition of complement pathways, inhibiting cytokine activating proteins, down regulation of MHC I molecules or interfering with proteosomal complexes.

3. Monitoring of viral infections

Development Team

Contents

1. Learning Outcomes

2. Introduction

3. Monitoring of viral infections

4. Role of cytokines in antiviral response

5. Role of Tetherin and Viperin

6. Role of APOBEC Family in innate immunity APOBEC

7. Role of RNA interference

8. Adaptive immunity to viral infection

9. How virus evade immune system.

10. Summary