Although there is no treatment for HTLV infection, asymptomatic HTLV-infected individuals should be routinely screened for evidence of disease progression and counseled on ways to avoid spreading the infection. There is no vaccine against HTLV infection or disease. The development of vaccines for retrovirus infections in general has proven extremely difficult.
Several experimental HTLV-1 vaccines have been designed that use the envelope portion of the virus as the immunogen. One HTLV-1 recombinant hybrid envelope product has been tested in cynomolgus monkeys.
Control monkeys and those with antibody titers below 20 developed signs of infection between 2 and 6 weeks after inoculation. Rabbits have been successfully immunized with vaccinia virus-env constructs. These products have not been tested in humans.
Because the development of adequate therapeutic approaches and vaccines may take many years, the most effective strategy to reduce the number of individuals with HTLV infection and disease is education. Initial infection with HIV may result in an acute syndrome with symptoms including fever, sweats, myalgia or arthralgia, sore throat, lymphadenopathy, nausea, vomiting, diarrhea, headaches, and rash Fig.
During the acute infection there may be a drop in the number of circulating T4 lymphocytes. It is not known what proportion of new HIV infections present with an acute syndrome and it is not clear that these symptoms are due to HIV, perse.
Often other infectious agents are co-transmitted with HIV. Following initial infection, there is a long and variable asymptomatic period. During this period there may be a slow, progressive decline in T4-cell numbers and an increase in T8 cells.
Some individuals may maintain relatively constant, normal levels of T4 cells during the asymptomatic period. The progressive immune deficiency is accompanied by a wide range of life-threatening opportunistic infections and neoplasms, the most common being Pneumocystis carinii pneumonia and Kaposi sarcoma, respectively.
This syndrome is characterized by neurologic abnormalities, including progressive dementia and peripheral neuropathy, and may occur in the absence of known opportunistic diseases. Clinical manifestations and pathogenesis of HIV infection. The general structure of HIV is similar to that of HTLV see above ; the virus consists of an external lipid bilayer glycoprotein envelope including envelope proteins gp and gp 41 , an internal protein core proteins p15, p17, and p24 , a viral RNA complexed with reverse transcriptase.
In addition to the structural gag, pol, and env genes and the regulatory tat analogous to HTLV tax and rev analogous to HTLV rex genes, the HIV-l genome contains at least four regulatory genes nef, vif, vpu, and vpr. HIV-2 does not have sequences for vpu, but does encode a novel gene, vpx, that is also found in the simian immunodeficiency virus.
HIV is classified as a retrovirus because it contains reverse transcriptase. It is a D-type virus in the Lentivirus family. Infection of cultured T4 cells with HIV usually results in cell death.
Two major antigenic types HIV-l and HIV-2 have been identified and are readily distinguished by differences in antibody reactivity to the envelope glycoprotein. The two HIV types share approximately 40 percent genetic identity. There is some disagreement about whether they are equally pathogenic. The most variable regions of the genome are in the env gene. This type of variation is also observed in HIV isolates obtained from individuals over the course of their infection.
HIV strains often display differences in replicative capacity and cytopathicity. The significance of these variations for the disease process is unclear. The first step in HIV infection is the high-affinity binding of the gp envelope glycoprotein to the CD4 receptor. The CD4 receptor is present on the surface of several cell types, including T4 cells and monocyte-macrophages. In contrast to HTLV infection, however, the final step in HIV replication often involves the budding of massive numbers of virions from the cell surface, resulting in cell lysis.
The high-affinity binding of the HIV envelope glycoprotein to the CD4 receptor is a crucial step in the pathogenesis of HIV, since the major cell expressing CD4 is the T4 lymphocyte often a helper cell.
The T4 cell plays a central role in all aspects of immune system function, so that death or impairment of this cell results in widespread immune dysfunction. There are several potential ways that HIV can damage T4 cells. In addition to direct cytopathicity, HIV infection may indirectly cause T4-cell death. One mechanism of indirect cell killing may involve autoimmune phenomena in which anti-HIV immune responses are targeted to uninfected T4 cells that either have free envelope protein bound to their membrane or present processed envelope antigens.
In addition, since both the HIV envelope protein and the class II major histocompatibility complex antigens bind to the CD4 receptor, their common binding sites may represent cross-reacting antigens. Therefore, anti-HIV antibodies may react with uninfected T4 cells that express class II major histocompatibility complex molecules. Also, it is very likely that anti-HIV immune effectors kill many infected cells. HIV-infected individuals usually exhibit immune dysfunction prior to a depletion of their T4 cells.
HIV may induce these functional abnormalities by a variety of pathways not necessarily involving a spreading infection of T4 cells.
For example, by binding to the CD4 receptor, HIV or its envelope protein can interfere with the CD4-mediated monocyte-T-cell interactions that are necessary for antigen-specific responses.
In addition, crosslinking of the CD4 molecules by the envelope protein may render the cell nonresponsive to subsequent antigenic stimulation. During the long asymptomatic period of HIV infection, the virus resides predominantly in a latent state and at low-level chronic form within lymph node T4 cells and, to a lesser extent, within monocytes-macrophages.
The mechanisms by which the virus is maintained in this relatively quiescent state are unclear. Similarly, little is known about the events that provoke activation.
In vitro, a number of factors have been identified that are associated with the activation of HIV expression. These factors include antigens, mitogens, cotransfection, or coinfection of heterologous viruses, and cytokines. It is thought that HIV upregulation by these factors involves the induction of cellular proteins that bind to the promotor region of the HIV DNA and boost its expression. The monocyte-macrophage is a target cell for HIV infection both in vivo and in vitro.
Infection of these cells may occur through the CD4 receptor or via phagocytosis. In contrast to T4 cells, monocyte-macrophages appear to be resistant to cell lysis.
Moreover, the virus can replicate intracellularly in monocyte-macrophages, with virions budding into intracytoplasmic vesicles. As a result, viral antigens may not be expressed on the cell surface, potentially enabling the monocyte-macrophages to escape immune surveillance and to transport the infection to other organ systems, particularly the lungs and brain.
Although the mechanisms by which HIV induces neuropsychiatric abnormalities are unknown, the macrophage is thought to play an important role. HIV infection in the brain appears to be largely restricted to macrophages, which may indirectly damage neuronal tissue by releasing neurotoxic factors or factors that induce inflammation. HIV may also interfere with the binding of neurotropic factors to their receptors on neurons. Another mechanism of HIV-induced neuropathology may involve autoimmune phenomena.
Clearly, some fraction of the neurologic abnormalities in HIV-induced disease is due to the wide range of opportunistic infections and tumors that afflict AIDS patients.
Although other retroviruses can directly cause cancers, HIV does not transform cells in vivo or in vitro. Antibodies to both the structural and regulatory proteins of HIV generally appear several weeks to months after initial infection. During the progression of HIV infection, antibody titers to the p24 core antigen decline, while antibody titers to the envelope protein remain relatively constant. Interferon has been found in some AIDS patients, but coinfecting opportunistic viruses may be responsible.
Since it is thought that HIV ultimately causes a slowly progressive, persistent infection in all infected individuals, the role of immune responses in preventing HIV-induced disease is unclear.
The emergence of genetic variants of HIV in vivo during the disease may be one way that HIV evades both humoral and cellular immune responses. HIV-1 infection has been reported throughout the world in both developed and developing countries. In the United States and other developed countries, HIV infection is found predominantly in homosexual and bisexual men and intravenous drug users.
Hemophiliacs, transfusion recipients, sexual partners of infected persons, and infants born to infected mothers are also at high risk. In many parts of Africa and the Caribbean, HIV-1 is found predominantly in heterosexuals, transfusion recipients, and infants born to infected mothers. Both HIV-1 and HIV-2 are spread through sexual contact, exposure to contaminated blood or blood products, and perinatally from an infected mother to her offspring.
It is estimated that as of , between , and 1. It is not known what proportion of these individuals will develop AIDS. The median incubation period is thought to be approximately 10 years. HIV infection is determined by the presence of HIV-specific antibodies, which usually occur weeks after infection. An HIV enzyme-linked immunosorbent assay is commonly used as the initial screening assay, but the current FDA-approved assays may miss many early-infected people.
There are sporadic reports of individuals in whom anti-HIV antibodies could not be detected for several years after infection. An individual is considered to be infected with HIV if a positive assay is confirmed by a positive Western blot or a similar, more specific assay. Detection of virus nucleic acid by the polymerase chain reaction may be used to diagnose HIV infection in antibody-negative individuals. AIDS is diagnosed predominantly on the basis of opportunistic infections or cancers indicative of a T4 cell defect in the absence of a known cause of immunodeficiency.
Neuropsychiatric manifestations are also indicative of AIDS. Although neurologic complications may arise from opportunistic infections of the central nervous system, tumors, and vascular problems, AIDS may present in the absence of these conditions as an HIV encephalopathy that is diagnosed by clinical findings of cognitive or motor dysfunction that interferes with daily activities.
AIDS may also be diagnosed in an HIV-infected individual on the basis of unexplained weight loss with either chronic diarrhea or chronic weakness and fever, known as HIV wasting syndrome. Strategies for the control of HIV infection and disease are similar to those for HTLV infection: therapy, education and public health, and vaccination.
Therapeutic categories for HIV include antiviral therapies, immune modulators, and therapies to treat and prevent opportunistic diseases. Serveral nucleoside analogs, are currently the only anti-HIV agents that have been shown to significantly improve survival in AIDS patients. Classification of viruses at the species level is difficult for several reasons. In particular, viruses do not sexually reproduce in any conventional sense, and it is difficult to identify a population of virions which make up a genetically distinct pool.
Thus, the definition of individual species is often controversial and is not necessarily aided by the criteria used to define larger phylogenetic groups. The translation products, together with progeny RNA, are assembled at the cell periphery into viral particles that are released from the cell by budding of the plasma membrane. Budding of viruses is followed by proteolytic cleavage of virion polyproteins by a viral protease and by cellular proteases.
Productive Retroviral infection is not of necessity cytopathic; infected cell cultures often show no visible effects of viral production. In some congenital infections in animals, virus can be produced by most cells in most tissues without deleterious effect on the development and function of the organism Rubin et al. In the replication cycle, viral entry, assembly, and release follow common patterns pathways similar to these events in other enveloped RNA viruses.
The unique steps in the retroviral growth cycle are reverse transcription and, especially, integration. Reverse transcription generates a progenitor proviral DNA copy from which the entire viral progeny of the cell is derived by polymerase-II-mediated transcription.
Although reverse transcription is much more error prone than cellular DNA replication, its product, once integrated into the cellular genome, has the genetic stability of cellular genes. This insertional mutagenesis can inactivate or activate cellular genes; this process is one of the Mechanisms by which retroviruses induce tumors.
Retroviruses have also developed unique mechanisms of pathogenicity involving the transfer or transcriptional activation of specific cellular genes. These Mechanisms are based on genetic recombination between virus and cell and between viral genomes. They are diploid and are the only viruses so equipped Billeter et al. A direct consequence of diploidy is the formation of heterozygote virions in cells that are infected with two or more genetically distinct but related retroviruses.
Such heterozygotes give rise, in the next cycle of infection, to stable genetic recombinants that are formed during the process of reverse transcription of the two parental genomes from the same viral particle. Rates of recombination between related retroviruses are high Coffin ; Linial and Blair ; Temin Interviral genetic exchange, together with integration into the cellular genome, formally also a recombination event, probably accounts for the presence of cellular genes in some retroviruses Fig.
A plausible hypothesis for this acquisition of cellular genetic material postulates that a provirus integrates upstream of a cellular gene and leads to the production of chimeric virus-cell transcripts. In the next round of replication, nonhomologous recombination between virus and cell sequences leads to the incorporation of the cellular gene into the retroviral genome, so that it is now transported by the virus from cell to cell and expressed under control of the viral LTR Goldfarb and Weinberg ; Swanstrom et al.
The usual product of this transduction process has acquired the host sequence at the cost of one or more viral genes. Such viruses are therefore generally defective for replication, requiring the presence of a replication-competent provirus in the same cell to provide viral proteins for replication see Fig. The transduction of cellular genes has been found only with simple retroviruses and not with complex retroviruses.
The reasons for this difference are not clear, but they may have to do with the mechanism by which retroviruses acquire cellular sequences or with viral genome organization that must be tolerant of foreign inserts. Retroviral transformation and oncogene transduction. From the top right: Infection of a cell with a retrovirus that contains only viral genes can occasionally initiate tumor formation by insertion more The modified cellular genes carried by retroviruses convey a high degree of tumorigenicity to the virus.
These viral or v- onc genes are usually mutated growth-regulatory genes. Their cellular progenitors are referred to as Protooncogenes or c- onc genes Bishop ; Varmus ; Cooper Overexpression or inappropriate expression, often combined with mutation of an oncogene that has become part of a viral genome, results in a gain of function of a positive growth signal. This constitutive gain of function induces and maintains malignant transformation.
Retrovirus vs Virus. Viruses are the first biological structures observed from an electron microscope, since they were not visible under the light microscope. They are the smallest living organism and do not have a proper cellular structure. Viruses need living organism to reproduce, and called obligate endoparasites Taylor et al, They are not either living or nonliving organism and held in between.
Viruses are the host specific, and out of the cell they are metabolically inert. Virus causes diseases to animals, plants, and bacteria.
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