STRUCTURAL FEATURES OF VIRUS Prokaryotes include several kinds of microorganisms, such as bacteria and cyanobacteria. Eukaryotes include such microorganisms as fungi, protozoa, and simple algae. Viruses are considered neither prokaryotes nor eukaryotes because they lack the characteristics of living things, except the ability to replicate (which they accomplish only in living cells). A.Virus Structure All viruses contain the following two components: 1) A nucleic acid genome 2) A protein capsid that covers the genome. Together this is called the nucleocapsid. In addition, many animal viruses contain a 3) Lipid envelope. The entire intact virus is called the virion. The structure and composition of these components can vary widely. 1. Viral Genomes: While the genomes of all known cells are comprised of double stranded DNA, the genomes of viruses can be comprised of single or double stranded DNA or RNA. They can vary greatly in size, from approximately 5-10 kb (Papovaviridae, Parvoviridae, etc.) to greater than 100-200 kb (Herpesviridae, Poxviridae). The known structures of viral genomes are summarized below. DNA: Double Stranded - linear or circular Single Stranded - linear or circular Other Structures - gapped circles RNA: Double Stranded - linear Single Stranded - linear : These single stranded genomes can be either + sense, - sense, or ambisense The sense strand is the one that can serve directly as mrna and code for protein, so for these viruses, the viral RNA is infectious. The viral mRNA from - strand viruses is not infectious, since it needs to be copied
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STRUCTURAL FEATURES OF VIRUS
Prokaryotes include several kinds of microorganisms, such as bacteria and cyanobacteria. Eukaryotes include such microorganisms as fungi, protozoa, and simple algae. Viruses are considered neither prokaryotes nor eukaryotes because they lack the characteristics of living things, except the ability to replicate (which they accomplish only in living cells).
A.Virus Structure All viruses contain the following two components: 1) A nucleic acid genome 2) A protein capsid that covers the genome. Together this is called the nucleocapsid. In addition, many animal viruses contain a 3) Lipid envelope. The entire intact virus is called the virion. The structure and composition of these components can vary widely.
1. Viral Genomes:
While the genomes of all known cells are comprised of double stranded DNA, the genomes of viruses can be comprised of single or double stranded DNA or RNA. They can vary greatly in size, from approximately 5-10 kb (Papovaviridae, Parvoviridae, etc.) to greater than 100-200 kb (Herpesviridae, Poxviridae). The known structures of viral genomes are summarized below. DNA: Double Stranded - linear or circular
Single Stranded - linear or circular
Other Structures - gapped circles
RNA: Double Stranded - linear
Single Stranded - linear : These single stranded genomes can be either + sense, - sense, or ambisense The sense strand is the one that can serve directly as mrna and code for protein, so for these viruses, the viral RNA is infectious. The viral mRNA from - strand viruses is not infectious, since it needs to be copied into the + strand before it can be translated. In an ambisense virus, part of the genome is the sense strand, and part is the antisense. The genome of some RNA viruses is segmented, meaning that a virus particle contains several different molecules of RNA, like different chromosomes.
Table: Types of nucleic acid, there structure and example
Nucleic Acid type Nucleic Acid structure Virus ExampleDNASingle-Stranded Linear single strand
Circular single strandParvovirusesΦX174, M13,fd phase
Reovirus, wound-tumor virus of plants, phage Φ6, many mycoviruses
2. Protein Capsid
Viral genomes are surrounded by protein shells known as capsids. A capsid is almost always made up of repeating structural subunits that are arranged in one of two symmetrical structures, a helix or an icosahedron. In the simplest case, these "subunits" consist of a single polypeptide. In many cases, however, these structural subunits (also called protomers) are made up of several polypeptides. Both helical and icosahedral structures are described in more detail below. Capsid is protein coat and Capsomeres are subunits of the capsid. Protomeres are capsomere subunits.
Helical Capsids : The first and best studied example is the plant tobacco mosaic virus (TMV), which contains a SS RNA genome and a protein coat made up of a single, 17.5 kd protein. This protein is arranged in a helix around the viral RNA, with 3 nt of RNA fitting into a groove in each subunit. Helical capsids can also be more complex, and involve more than one protein subunit.
A helix can be defined by two parameters, its amplitude (diameter) and pitch, where pitch is defined as the distance covered by each turn of the helix. P = m x p, where m is the number of subunits per turn and p is the axial rise per subunit. For TMV, m = 16.3 and p= 0.14 nm, so P=2.28 nm. This structure is very stable, and can be dissociated and re-associated readily by changing ionic strength, pH, temperature, etc. The interactions that hold these molecules together are non-covalent, and involve H-bonds, salt bridges, hydrophobic interactions, and van-der Waals forces. Several families of animal virus contain helical nucleocapsids, including the Orthomyxoviridae (influenza), the Paramyxoviridae (bovine respiratory syncytial virus), and the Rhabdoviridae (rabies).
Icosahedral Capsids : In these structures, the subunits are arranged in the form of a hollow, quasi spherical structure, with the genome within. An icosahedron is defined as being made up of 20 equilateral triangular faces arranged around the surface of a sphere. They display 2-3-5 fold symmetry as follows:
- An axis of 2 fold rotational symmetry through the center of each edge.
- An axis of 3 fold rotational symmetry through the center of each face.
- An axis of 5 fold rotational symmetry through the center of each corner.
These corners are also called Vertices, and each icosahedron has 12.
Since proteins are not equilateral triangles, each face of an icosahedron contains more than one protein subunit. The simplest icosahedron is made by using 3 identical subunits to form each face, so the minimum of subunits is 60 (20 x 3).
Many viruses have too large a genome to be packaged inside an icosahedron made up of only 60 polypeptides (or even 60 subunits), so many are more complicated. In these cases, each of the 20 triangular faces is divided into smaller triangles; and each of these smaller triangles is defined by 3 subunits. However, the total number of subunits is always a multiple of 60. The total number of subunits can be defined as 60 X N, where N is sometimes called the Triangulation Number, or T. Values for T of 1,3,4,7,9, 12 and more are permitted.These are usually protein subunits clustered around an axis of symmetry, and have been called "morphological units" or capsomers.
3.Viral Envelope
In some animal viruses, the nucleocapsid is surrounded by a membrane, also called an envelope. This envelope is made up of a lipid bilayer, and is comprised of host-cell lipids. It also contains virally encoded proteins, often glycoproteins which are trans-membrane proteins. These viral proteins serve many purposes, such as binding to receptors on the host cell, playing a role in membrane fusion and cell entry, etc. They can also form channels in the viral membrane.
Many enveloped viruses also contain matrix proteins, which are internal proteins that link the nucleocapsid to the envelope. They are very abundant (ie, many copies per virion), and are usually not glycosylated. Some virions also contain other, non-structural proteins that are used in the viral life cycle. Examples of this are replicases, transcription factors, etc. These non-structural proteins are present in low amounts in the virion.
Enveloped viruses are formed by budding through cellular membranes, usually the plasma membrane but sometimes an internal membrane such as the ER, golgi, or nucleus. In these cases, the assembly of viral components (genome, capsid, matrix) occurs on the inside face of the membrane, the envelope glycoproteins cluster in that region of the membrane, and the virus buds out. This ability to bud allows the virus to exit the host cell without lysing, or killing the host. In contrast, non-enveloped viruses, and some enveloped viruses, kill the host cell in order to escape.
Fig. Virus structure
4.Taxonomy of Viruses 1) Orders (virales): Groupings of families of viruses that share common characteristics and are distinct from other orders and families.
2) Families (-viridae): Groupings of genera of viruses that share common characteristics and are distinct from the member viruses of other families.
3) Subfamilies (-virinae): Not used in all families, but allows for more complex hierarchy of taxa.
4) Genera (-virus): Groupings of species of viruses that share common characteristics and are distinct from the member viruses of other species.
5) Species (virus); The definition accepted by ICTV is "a virus species is defined as a polythetic class of viruses that constitutes a replicating lineage and occupies a particular ecological niche". A species can be further broken down into strains, variants, etc.
Viral Size: It is determined by electron microscopy. Ranges from 20 to 14,000 nm in length.There is also a group of giant viruses, including the giant mimivirus, which is something like 800 nm in diameter and has a genome with 1.2Mbp base pairs carrying somewhere in the neighborhood of 1000 genes, 911 of which code for proteins.
Fig. Various size of virus
The Isolation, Cultivation and Identification of Viruses Viruses must be grown in living cells. They can't be grown in culture media or on agar plates alone, they must have living cells to support their replication.The easiest viruses to grow are bacteriophages (because the easiest cells to grow in the lab are bacteria).
Bacterial viruses or bacteriophages (phages for short) are cultivated in either broth or agar cultures of young, actively growing bacterial cells. So many host cells are destroyed that turbid bacterial cultures may clear rapidly because of cell lysis. Complex bacterial viruses with both heads and tails are said to have binal symmetry because they possess a combination of icosahedral (the head) and helical (the tail) symmetry. Most of the phages are double-stranded DNA viruses. Some contain single-stranded DNA and single and double –stranded RNA genome.Few examples of phages and their nature of the genome are given below:
Nature of genome ExampleSingle stranded DNA ФX174, fdDouble stranded DNA T-phages , λ-phagesSingle –stranded RNA genome MS2 Of plus sense Double–stranded RNA Ф6
Growing bacteriophages in the laboratory
Once viruses have replicated and been harvested the concentration of viral particles (virions) in the viral stock solution must be determined. One of the easiest ways to determine the concentration of a stock solution of bacteriophages is to use the plaque method.
The plaque method: Virus, bacteria, and agar mixed, plated and incubated.After replication the virus lyses the bacteria, forming plaques, or clear zones. Each plaque is assumed to come from a single viral particle.The titer (concentration of the stock solution) of the virus is given in plaque forming units.
Growing Animal Viruses In The Laboratory Embryonated eggs can serve as substitutes for some viruses.Inoculate membrane that best supports specific virus (allantoic, amniotic,
chorioallantoic, or yolk sac).
Cell culture is a lot cheaper and easier to work with (contamination can be a problem however). Primary cell lines have a short lifespan in culture – a few generations before reaching senescence. Diploid cell lines are derived from embryos and can grow for up to 100 population doublings before senescence. Continuous cell lines are derived from transformed cells and grow indefinitely in culture (Fig.).
Hela cells – 1st continuous cell line, derived from Helen Lane (fictional name - actually named Henrietta Lacks), a cervical cancer patient who died in 1951. This is the oldest continuous cell line and was first used to culture and identify polio virus.
Fig. Transformed cells and grow indefinitely in culture
Viral growth can cause cytopathic effects in the cell culture. Cytopathic effects can appear early or late in the course of the viral infection. Cytopathic effects may be cytocidal (cell death) or non-cytocidal. Non-cytocidal effects include acidophilic or basophilic inclusion bodies in the nucleus, cytoplasm, or both; cell fusion, and transformation. Cytopathic effects can be so characteristic of individual viruses that they can often be used to identify viruses.
Viral Identification Serological methods Western blotting Cytopathic effects
Diagnostic inclusion bodies are associated with rabies virus, measles virus, vaccinia virus, smallpox virus, herpesvirus, and adenoviruses.
Molecular methods include PCR and RFLPs. PCR was used to identify the West Nile virus and the SARS-associated coronavirus
Viral Multiplication
Viruses do not contain enzymes for energy production or protein synthesis. For a virus to multiply, it must invade a host cell and direct the host’s metabolic machinery to produce viral enzymes, viral proteins, and copies of its nucleic acid, using the host cell's ATP to power the reactions. Viral particles disappear upon penetration, none are seen during biosynthesis and assembly, and eventually all cells die so no new virions can be produced. The eclipse period is the period when all viral particles are present but before they are assembled.
Fig. Viral multiplication cycle
Burst time is the time from phage adsorption to release.Burst size is the number of newly synthesized phages produced from one infected cell.
5.Multiplication of Bacteriophages
The virus may cause lysis or lysogeny.
A. lytic cycle:
Attachment or adsorption: Requires a receptor
Penetration: T-evens release lysozyme to break down a portion of the cell wall. The tail sheath contracts and the tail core is driven through the hole in the wall to the plasma membrane.The viral genome is then injected into the bacterium.
Biosynthesis: Viral DNA and proteins are synthesized. Host protein synthesis is stopped by degradation of host DNA, interference with transcription, or repression of translation.
Maturation: During maturation or assembly phage DNA and capsids are assembled into complete viruses.
Release: Release occurs when phage lysozyme breaks down the cell wall and newly synthesized phage particles are released.
B.Lysogeny
It is a cycle in which the phage DNA recombines with the bacterial chromosome. The incorporated viral DNA is now a prophage. The prophage genes are regulated by a repressor coded for by the prophage, the prophage is replicated each time the host DNA is replicated. Exposure to mutagens can lead to excision of the prophage and initiation of the lytic cycle.
Table: Bacteriophage and viral multiplication compared
Fig. Lytic cycle
Fig. Lysogenic cycle
Viruses and Cancer
Several pieces of evidence pointed to the transmission of cancer by viruses in animals.
1908 - Chicken leukemia
1911 - Rous chicken sarcoma
1936 - Virus-induced adenocarcinoma in mice
1972 - First human cancer-causing virus discovered and isolated.
Transformation Of Normal Cells Into Tumor Cells
Oncogenes - genes involved in tumor formation, first identified as part of viral genomes. It was later shown that the viral oncogenes were actually derived from animal cells.
Oncogenes may be activated (to function abnormally or without normal controls) by mutagenic chemicals, radiation, and viruses. Activation events may include mutation, transduction, translocation, and amplification.
Oncogenic viruses are capable of producing tumors in animals. Oncogenic viruses integrate into host cell DNA and may cause transformation of host cells.Transformed cells lose contact inhibition, contain virus-specific antigens (tumor-specific transplantation antigen (TSTA)on the cell surface or T antigen in the nucleus), exhibit chromosomal abnormalities, and can produce tumors when injected into susceptible animals.
Tumor Types :
Benign - tumors that generally don’t spread, can be removed, and aren’t life threatening
Malignant – invasive, generally aggressive tumors that are life threatening
Characteristics of Benign and Malignant Tumors
Organization (differentiation and anaplasia)
Differentiation: the extent to which tumor cells resemble the cell of origin in both appearance and function
Anaplasia: undifferentiated, cells appear almost embryonic Pleomorphism: variation in shape and size Dysplasia: disorganized but non-neoplastic
The relationship between anaplasia and growth rate and specialized function is inverse the more anaplastic and the faster growing cells are the less likely to have specialized function. Benign tumors tend to be more differentiated, exhibit dysplasia, and the cells aren't usually pleomorphic. Malignant tumors tend to exhibit anaplasia and pleomorphism.
Rate of growth
Benign tumors generally grow slowly. Malignant tumors exhibit a correlation between rate of growth and degree of differentiation. May have periods of slow growth followed by rapid growth, may spontaneously regress to due central necrosis and inability to provide nutrition
Local invasion
Benign tumors are usually demarcated and often encapsulated. Malignant tumors are invasive; penetrate surrounding tissue
Metastasis
Development of secondary tumors distant from the site of the original tumor, characteristic of malignant tumors
DNA Oncogenic Viruses
– Adenoviruses
– Herpesviruses
EBV: Burkitt’s lymphoma, Nasopharyngeal carcinoma Herpes simplex: Association with cervical cancer
– HIV– HTLV-1 and HTLV-2 are associated with human leukemia and lymphomas.Reverse
transcriptase produces viral DNA that integrates into host genome as a provirus.
Latent Viral Infections
Many viruses, especially the human herpesviruses, can remain in host cells throughout life without causing disease. They may be reactivated by immunosuppression, however, and cause disease.
Examples: Cold sores, Shingles
Persistent Viral Infections
Persistant viral infections (formerly termed slow viral infections) are progressive over a long period of time and are usually fatal. Persistant viral infections are different from latent viral infections in that the detectable virus builds slowly over a long period of time rather than appearing suddenly.
Table: Example of latent and persistent viral infections in human
Fig. Graph between number of virions and time
Prions
Prions are infectious proteins. Insoluble aggregates of protein with normal primary sequence but exhibit altered folding pattern. The normal protein (PrPc) is coded for by a gene on chromosome 20. The abnormal form (PrPSc) is found in disease states. Abnormally-folded proteins (PrPsc)
cause normal proteins to assume the pathogenic conformation. The diseases are spongiform encephalopathies that cause large vacuoles to appear in the brain.
Fig. Process of prions toward to normal to abnormal form and result is cell death
Diseases:
– Scrapie (sheep)– Transmissible mink encephalopathy– Bovine spongiform encephalitis (mad cow disease)– Kuru – New Guinea, contracted by eating infected brain tissue (cannabilism was a
mourning rite among members of this particular tribe between about 1920 and 1950)– Creutzfeldt-Jakob disease (CJD) is very similar and has a heritable form and may be
– Coconut cadang-cadang– Cherry chloratic mottle– Cucumber pale fruit disease
Table: Classification of some plant viruses
Viroids are naked (lacking a protein coat) pieces of RNA that can cause some plant diseases. They are internally base paired, so they assume a folded conformation that protects them from enzymatic degradation.
Viroids don't code for proteins and research indicates that they have similarities to introns, which suggests researchers may discover animal viroids in the future.
Human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS) is a disease spectrum of the human immune system caused by infection with human immunodeficiency virus (HIV). AIDS was first recognized by the United States Centers for Disease Control and Prevention (CDC) in 1981in the Los Angeles , New York, and San Francisco when a group of patients displayed pneumocystis carinii pneumonia(PCP), caused by opportunistic fungal pathogen pneumocystis carinii and Kaposi sarcoma, an extremely rare skin tumor. A more complete evaluation of the patients showed that they had in common a marked deficiency in cellular immune responses and a significant decrease in the sub population of T-cells that carry the CD4 marker. The CD4 molecule is 55kDa protein found predominantly on a subset of T-lymphocytes that are responsible for helper or inducer function in the immune system. It is also expressed on the surface of monocytes/macrophages.
Etiologic agent of AIDS is immunodeficiency Virus(HIV). It was discovered and characterized by Luc Montagneir (in paris) and Robert Gallo in the year 1983 from a patient suffering from lymphadenopathy. HIV belongs tp the family of human retrovirus and the subfamily of lentiviruses. AIDS is caused primarily by the HIV-1 virus. This virus is closely related to HTLV-I, the cause of adult T-cell leukemia, or disabling progressive neurologic disorder called HTLV-I associated myelopathy and HTLV-II, which has been isolated from individuals with hairy-cell leukemia.
Recently, a virus Simian Immunodeficiency Virus(SIV) related to HIV-1 and HIV-2 has been isolated from African green monkey and is believed to the ancestor of the HIV. Somehow, this virus entered in humans and mutated to the two current African human viruses SBL and IAV-2, which are intermediate viruses, these intermediate viruses may have evolved into the highly virulent HIV-1 . HIV was formely called lymphadenophathy associated virus (LAV), human T Lymphotropic viruses (HTLV-III) and AIDS associated retrovirus (ARV).
Structure of HIV-1
HIV-1 has an icosahedral structure. It is an enveloped lentivirus within the family retroviridae. HIV infects mainly the CD4+ lymphocytes (T cells), but also to a lesser degree monocytes, macrophages, and dendritic cells (these cells are also CD4+ cells). Once infected, the cell turns into an HIV-replicating cell and loses its function in the human immune system.The envelope is derived from the host cell. An HIV virus particle is spherical and has a diameter of about 1/10,000 mm. The envelope contains 72 external spikes, made up of glycoproteins gp 120(external) and gp41 (transmembrane). Gp stands for glycoprotein and the number refers to the mass of protein, in thousands of Daltons. These glycoprotein serves as the viral receptor for CD4 on the host cells. Within the envelope is the viral core ,or nucleocapsid, which includes two layers of a protein-an outer layer called p17 and an inner layer called p24.
Fig. Anatomy of the AIDS Virus
HIV genome:
HIV-1 is a retrovirus. It contains two copies of plus single stranded RNA genome. Most retroviruses that are capable of replication contain only three genes namely gag, pol and env. HIV-1 contains nine different genes in its 9kb RNA genome (gag, pol, env, vif, vpu vpr, tat, rev and nef). Flanking these genes are the Long Terminal Repeats (LTR), Which contain regulatory elements involved in gene expression. The major difference between the genome of HIV-1 and HIV-2 is that HIV-2 lacks the vpu gene and has a vpx gene not contained in the HIV-1.
Gene Function of encoded proteingag Nucleocapsid proteinspol Enzymes like reverse trancripatase, protease, integrase, ribonucleaseenv Envelope glycoproteinvif Promotes infectivity of voral particlevpu Required for efficient viral assembly and buddingvpr Weakly activates transcription of proviral DNAtat Strongly activates transcription of proviral DNArev Allows export of unspliced and singly spliced mRNAs from nucleusnef Increases viral replication down-regulates host–cell CD4
Life cycle of HIV
HIV can infect multiple cells in your body, including brain cells, but its main target is the CD4 lymphocyte, also called a T-cell or CD4 cell. When a CD4 cell is infected with HIV, the virus goes through multiple steps to reproduce itself and create many more virus particles.
The process is broken up into the following steps:
1. Binding and Fusion: This is the process by which HIV binds to a specific type of CD4 receptor and a co-receptor on the surface of the CD4 cell. This is similar to a key entering a lock. Once unlocked, HIV can fuse with the host cell (CD4 cell) and release its genetic material into the cell.
2. Reverse Transcription: A special enzyme called reverse transcriptase changes the genetic material of the virus, so it can be integrated into the host DNA.
3. Integration: The virus’ new genetic material enters the nucleus of the CD4 cell and uses an enzyme called integrase to integrate itself into your own genetic material, where it may “hide” and stay inactive for several years.
4. Transcription: When the host cell becomes activated, and the virus uses your own enzymes to create more of its genetic material along with a more specialized genetic material which allows it make longer proteins.
5. Assembly: A special enzyme called protease cuts the longer HIV proteins into individual proteins. When these come together with the virus’ genetic material, a new virus has been assembled.
6. Budding: This is the final stage of the virus’ life cycle. In this stage, the virus pushes itself out of the host cell, taking with it part of the membrane of the cell. This outer part covers the virus and contains all of the structures necessary to bind to a new CD4 cell and receptors and begin the process again.
These steps of the life-cycle of HIV are important to know because the medications used to control HIV infection act to interrupt this replication cycle.
HIV-1 infects T-cells that carry the CD4 antigen on their surface; in addition certain HIV strains will infect monocytes and other cells that have CD4 on their surface. Binding to CD$ on the cell surface and viral entry is also mediated by Chemokine co-receptors CXCR4 or fusin and CCR5 present on T-cell and monocytes, respectively.
After the virus has entered the cell, the RNA genome of the virus is reverse transcribed and translate into proteins, which along with a complete new copy of the RNA genome are used to form new viral particles.
Infection of target cell:
HIV gp120 binds to CD4 on target cell. Fusogenic domain in gp41 and CXCR4, a GPCR in the target-cell membrane, mediate
fusion. Nucleocapsid containing viral genome and enzymes enter cells. Viral genome and enzymes are released following removal of core proteins. Viral reverse transcriptase catalyzes reverse transcription of ssRNA, forming RNA-DNA
hybrid. Original RNA template is partially degraded by ribonucleases H, following by synthesis
of the second DNA strand to yield HIV dsDNA. The viral dsDNA is then translocated to the nucleus and integrated randomly into the host
chromosomal DNA by the viral integrase enzyme.Activation of provirus:
Transcription factors stimulate transcription of proviral DNA into genomic ssRNA and after processing several mRNAs.
Viral RNA is exported to the cytoplasm. Host-cell ribosomes catalyze the synthesis of viral precursor proteins. Viral proteases cleave precursors into which gp41 and gp120 are inserted. The membrane buds out, forming the viral envelope. Released viral particles complete maturation; incorporated precursor protein are cleaved
by the viral protease present in viral particles.Therapeutic agents:
At present there is no complete cure for AIDS. Primary treatment is directed at reducing the viral load and disease symptoms, and at treating opportunistic infection and malignancies. The antivirals currently approved for use in HIV disease are of two types.
Reverse transcriptase inhibitors are nucleoside analogous that inhibit the enzyme reverse transciptase as it. Synthesizes DNA from RNA. Examples include AZT or zidovudine (Retrovir), didanosine(Videx), zalcitabine(HIVID), stavudine, lamivudine, delavirdine and nevirapine ( viramune).
Protease inhibitors work by blocking the activity of the HIV protease and thus interfere with virion assembly. Examples include indinavir (Crixivan), ritonavir, nelfinavir( viracept), and saquinavir (Invirase). However, the most successful treatment approach is to use drug combinations. An effective combination is a cocktail of AZT, lamirudine, and a protease inhibitor such as ritonavir.
Stages of HIV infection:Antiretroviral therapy (ART) prevents the HIV virus from multiplying and from destroying your immune system.
a.Acute infection stageWithin 2-4 weeks after HIV infection, many people develop flu-like symptoms can include fever, swollen glands, sore throat, rash, muscle and joint aches and pains, fatigue, and headache. This is called “acute retroviral syndrome” (ARS) or “primary HIV infection,” and it’s the body’s natural response to the HIV infection.
b.Clinical latency stageAfter the acute stage of HIV infection, the disease moves into a stage called the “clinical latency” stage. “Latency” means a period where a virus is living or developing in a person without producing symptoms. During the clinical latency stage, people who are infected with HIV experience no HIV-related symptoms, or only mild ones. (This stage is sometimes called “asymptomatic HIV infection” or “chronic HIV infection.”)During the clinical latency stage, the HIV virus continues to reproduce at very low levels, although it is still active. If you take ART, you may live with clinical latency for several decades because treatment helps keep the virus in check.
c.AIDSThis is the stage of HIV infection that occurs when your immune system is badly damaged and you become vulnerable to infections and infection-related cancers called opportunistic infections. When the number of your CD4 cells falls below 200 cells per cubic millimeter of blood (200 cells/mm3), you are considered to have progressed to AIDS. (In someone with a healthy immune
system, CD4 counts are between 500 and 1,600 cells/mm3.) As HIV disease progresses in your body, you may notice physical changes. Some changes may occur as side-effects of medical treatment for HIV. Others may occur as a result of the impact that HIV (or AIDS) has on your body. The best treatment for HIV infection is Highly active antiretroviral therapy (HAART).
