The transmission dynamics of human immunodeficiency virus (HIV)

The paper first reviews data on HIV infections and AIDS disease among homosexual men, heterosexuals, intravenous (IV) drug abusers and children born to infected mothers, in both developed and developing countries. We survey such information as is currently available about the distribution of incubation times that elapse between HIV infection and the appearance of AIDS, about the fraction of those infected with HIV who eventually go on to develop AIDS, about time-dependent patterns of infectiousness and about distributions of rates of acquiring new sexual or needle-sharing partners. With this information, models for the transmission dynamics of HIV are developed, beginning with deliberately oversimplified models and progressing--on the basis of the understanding thus gained--to more complex ones. Where possible, estimates of the model's parameters are derived from the epidemiological data, and predictions are compared with observed trends. We also combine these epidemiological models with demographic considerations to assess the effects that heterosexually-transmitted HIV/AIDS may eventually have on rates of population growth, on age profiles and on associated economic and social indicators, in African and other countries. The degree to which sexual or other habits must change to bring the 'basic reproductive rate', R0, of HIV infections below unity is discussed. We conclude by outlining some research needs, both in the refinement and development of models and in the collection of epidemiological data.     

Removing human immunodeficiency virus (HIV) from human blood using immobilized heparin

Heparin covalently attached to a water-insoluble resin suspended in HIV-infected aqueous buffer or whole blood captures the virus; subsequent physical separation of the immobilized heparin reduced the viral titers by over 80 and 50%, respectively. The detoxification concept has been validated by both circulating an HIV-1 solution through a column packed with the heparin–sepharose beads and successively mixing an HIV-1 solution with fresh beads.     

Isolation of human immunodeficiency virus (HIV) from whole blood]

The authors describe a simple and sensitive technique for HIV isolation from small amounts of heparinized whole blood. This method demonstrated a high efficiency in detecting HIV at all stages of disease and appeared more sensitive with respect to viral isolation from peripheral blood mononuclear cells. Although further studies are needed to better understand the biological significance of a positive cultural result obtained by this method, HIV isolation from whole blood can be routinely employed, especially when small amounts of blood are available.     

Epidemic human immunodeficiency virus (HIV) infection among intravenous drug users (IVDU)

Human immunodeficiency virus (HIV) infection is epidemic among intravenous drug users (IVDU), particularly in the northeastern United States. IVDU are playing a critical role in the spread of HIV by infecting their heterosexual partners and children, as well as their needle-sharing partners. The epidemiology of HIV infection among IVDU is reviewed here, including a compilation of seroprevalence data. Relevant determinants of the future spread of HIV among IVDU are discussed, including the major risk factors for HIV seropositivity, the modes of HIV transmission, and aspects of the natural history of HIV infection in IVDU. The public health policy implications of these issues include the need for education of adolescents and the general public about the risks of drug injection and heterosexual intercourse with IVDU, as well as motivation of IVDU to stop injecting, never share injection paraphernalia, or, at least, clean needles effectively.     

On the origin and evolution of the human immunodeficiency virus (HIV)

The human AIDS viruses--HIV-1 and HIV-2--impose major burdens on the health and economic status of many developing countries. Surveys of other animal species have revealed that related viruses--the SIVs are widespread in a large number of African simian primates where they do not appear to cause disease. Phylogenetic analyses indicate that these SIVs are the reservoirs for the human viruses, with SIVsm from the sooty mangabey monkey the most likely source of HIV-2, and SIVcpz from the common chimpanzee the progenitor population for HIV-1. Although it is clear that AIDS has a zoonotic origin, it is less certain when HIV-1 and HIV-2 first entered human populations and whether cross-species viral transmission is common among primates. Within infected individuals the process of HIV evolution takes the form of an arms race, with the virus continually fixing mutations by natural selection which allow it to escape from host immune responses. The arms race is less intense in SIV-infected monkeys, where a weaker immune response generates less selective pressure on the virus. Such a difference in virus-host interaction, along with a broadening of co-receptor usage such that HIV strains are able to infect cells with both CCR5 and CXCR4 chemokine receptors, may explain the increased virulence of HIV in humans compared to SIV in other primates.     

Isolation and antigenic characterization of human immunodeficiency virus (HIV) in Brazil

A retrovirus infecting a Brazilian AIDS patient was isolated and characterized in terms of its reactivity with sera from individuals infected with human immunodeficiency viruses 1 and 2 (HIV-1 and HIV-2). The Western blot analysis revealed that the Brazilian isolate is very similar to the well characterized HIV-1 strain. The serum of the patient from whom the virus was isolated did not react with the 140 kDa envelope glycoprotein specific for HIV-2.     

Isolation of the human immunodeficiency virus (HIV) from the cerebro-spinal fluid

The authors describe a simple and available technique for HIV isolation from cerebrospinal fluid and report preliminary results obtained. Exposed data indicate that neurological involvement occurs early in the natural history of HIV infection and that the virus may be recovered in CSF at all stages of the disease, regardless of immunological conditions of patients. Virological evaluation of CSF may be important in understanding pathogenetic aspects of HIV infection and in clinical management of infected patients.     

Raman spectroscopic study on structure of human immunodeficiency virus (HIV) and hypericin-induced photosensitive damage of HIV

The first Raman spectra of HIV1-HIV2 in human sera and hypericin-induced photosensitive damage of the virus have been obtained. The prominent Raman lines in the spectra are assigned respectively to the carbohydrates of viral glycoprotein, RNA, protein and lipid. The spectra are dominated by Raman scattering of the carbohydrates. The lines of D-Mannose and N-acetylglucosamine in carbohydrates are obvious and there is a β-configuration in the anomeric C1 position in D-Mannose. The viral RNA duplexes bound assumes an A-form geometry. The lines of backbone phosphate group, bases (involving interbase hydrogen bonding) and ribose of the RNA are complete and distinct. The secondary structure of the viral protein maintains α-helix, β-sheet, β-turn and random coil. Its side chains are rich and vary from tryptophan, phenylalanine and “buried” tyrosine; the stable conformation of the S-S bond of gauche-gauche-gauche; the two forms of C-S bonds of gauche and trans; to sulfhydrl group and ionized and unionized carboxyl groups. The viral lipid bilayer molecules are probably in the liquid ordered phase or the gel phase. It was observed that the hypericin-induced photosensitive damage of HIV1-HIV2 in human sera changed various components of HIV1-HIV2 in different degrees: The orderly A-form viral RNA would become a disordered viral RNA. There were a breakage of interbase hydrogen bonds and disruption of vertical base-base stacking interactions. In addition, the groups of ribos and four bases were damaged obviously. A decrease in ordered structure (α-helix and β-sheet) of viral protein is accompanied by an increase in random coil. The Tyr buried in the three-dimensional structure of protein was damaged, but it was still “buried” and the damage of C-S bond of trans form was stronger. The groups of carbohydrates, including D-Mannos and N-acetyl glucosamine, in viral envelope glycoprotein had also been changed. The hydrophilic C-N bond of choline in viral lipid was damaged, which was the possible binding site to hypericin, whereas the viral lipids bilayers were still probably in the liquid ordered phase or the gel phase. So the space structure of HIV1-HIV2 was damaged under the experimental conditions, which might block viral infection and inhibit its growth and breeding. It is apparent that the laser Raman spectra have provided certain direct evidence at the molecular level for photosensitive damage of HIV1-HIV2.     

Raman spectroscopic study on structure of human immunodeficiency virus (HIV) and hypericin-induced photosensitive damage of HIV

Viruses are agents of some of the most destruc- tive diseases afflicting plants and animals[1]. Viruses also play a central role in experimental methods of molecular and cellular biology, especially in modern genetic engineering[1]. Raman spectroscopy is a pow-erful tool for studying the structure of the whole virion. A number of researches are limited to the conforma-tion of viruses, involving only nucleic acid (RNA or DNA) and its coat protein[1]. Literatures can be found concerning Raman…     

Focus formation by the human immunodeficiency virus (HIV) in the immobilized MT-4 cell culture and its application to the evaluation of anti-HIV agents.

Immunofluorescence studies were performed on the infection of monolayer cultures of immobilized MT-4 cells with human immunodeficiency virus type 1 (HIV-1). By using the anti-viral p24 monoclonal antibody, we could observe formation of foci of p24 antigen-positive cells within 3 to 4 days when the infection was initiated with a relatively small amount of the virus. Frequency of the focus formation was in proportion to the dose of input virus (ranging from 0.001 to 0.1 PFU/cell), which allowed us to apply this phenomenon to the assay of anti-HIV agents as well as to the estimation of relative infectivity of the virus stocks. When antiviral agents were added to the infected cultures, number of foci as well as the size of each focus was reduced in a concentration-dependent manner. The dose required for reducing the number of foci by 50% was calculated to be 6 ng/ml and 8 ng/ml for tunicamycin (TM) and azidothymidine (AZT), respectively. These values are comparable to those obtained by other current assay methods. In addition, focus reduction assay is also useful in searching for such antiviral agents that would inhibit or block the early step of viral replication cycle.     

Multiple centrosome formation induced by the expression of Vpr gene of human immunodeficiency virus.

We previously established a cell line called MIT-23 in which expression of the Vpr gene of human immunodeficiency virus 1 (HIV-1) can be controlled by the addition of tetracycline. Vpr expression induces multiple nuclear formation and increased ploidy in MIT-23 cells. We herein report that multipolar mitotic spindles were formed upon induction of Vpr. Further analysis of centrosomes with anti-gamma-tubulin immunostaining revealed that a significant population of cells 1 week after expression of Vpr gene product had an increased number of centrosomes in the cells with abnormal nuclei. Taking into account that the centrosome plays an important role in genome integrity, the abnormal number of centrosomes in cells expressing Vpr may be directly related to aneuploidy or the formation of micronuclei in MIT-23 cells, suggesting that Vpr has an oncogenic role in HIV infected cells.     

Principles of laboratory isolation and identification of the human immunodeficiency virus (HIV)

Diagnosis of human immunodeficiency virus (HIV) infections has relied most frequently on detecting the presence of HIV antibodies in sera. In many situations, however, patients management can be significantly improved if the presence of HIV can be demonstrated in patients' specimens. In this review, the need and value of HIV isolation for confirming the diagnosis of HIV, for disease staging, and for monitoring the effectiveness of antiviral therapy are discussed. The steps involved in isolation of HIV, the cell systems permissive to HIV growth, and the procedures for virus identification are reviewed. Furthermore, methods available for the direct detection of HIV in patients' specimens are summarized. Although isolation of HIV is presently an elaborate procedure, as easier methods become available, it will play a large role in the management of HIV-infected individuals.     

Syncytium-inducing capacity of human immunodeficiency virus (HIV): analysis by the use of cloned viruses

The marked cytopathic effects of human immunodeficiency virus HIV for susceptible cells are caused mainly by fusion between cells expressing viral envelope glycoproteins and cells expressing CD4 molecule. In this study, we tested the ability of different clones of HIV to induce syncytia in CD4-positive cells. We have reported marked difference in syncytium-inducing capacity of 2 clones of human T lymphotropic virus type III (HTLV-IIIB) isolate despite no detectable difference in expression of viral glycoprotein (gp120). This difference in syncytium induction could be explained by the difference detected in their infectivity and binding activities to CD4-positive cells. Meanwhile we reported difference in syncytium-inducing capacity of 2 clones of lymphadenopathy associated virus (LAV1) isolate parallel to the different amounts of gp120 and other viral proteins expressed by these 2 clones. These results suggest that viral factors like infectivity and binding affinity of the virus to the susceptible cells and the amount of viral gp120 expressed by the infected cells may interact in a complex manner affecting fusion activity and syncytium induction in CD4-positive cells.