Heterosexual spread of human immunodeficiency virus in Edinburgh

Heterosexual transmission of human immunodeficiency virus (HIV) was investigated in 123 subjects with no apparent risk factor for infection other than having had heterosexual intercourse with a person who was either infected with HIV or at high risk of being infected with it. Seven subjects were found to be infected with the virus. Risk factors for transmission included being the regular sexual partner of an abuser of intravenous drugs and having a sexual relationship of more than 18 months'' duration. Anal intercourse was not a risk factor in the three subjects who admitted to it. There were 41 regular partnerships with abusers of intravenous drugs in which the antibody state and history were fully known for both partners. In these partnerships male to female transmission of the virus occurred in five out of 34 (15%) and female to male in one out of seven. In 30 couples in whom one partner was known to be positive for HIV and an abuser of intravenous drugs four female partners were found to be seropositive at first testing, but there were no new positive results on subsequent serial testing. In six of these 30 couples both partners abused intravenous drugs but the partner who was negative for HIV remained so. Few of the partnerships always practised safe sexual techniques, even after a partner was known to be positive for HIV.Heterosexual transmission of HIV occurred but was incomplete and may be related to the timing of the relationship with the infection.     

The immunology of the infection caused by the human immunodeficiency virus

In this work the data contained in the literature and obtained by the author are presented. These data may change the traditional concepts of the immunopathology of AIDS. The analysis of these data indicates that the explanation of disturbances in the immune system, attributing their cause to the cytocidal action of HIV, is simplified. HIV may infect cells containing no antigen CD4. Perhaps, the fusion of gp41 with the membrane of the target cells is necessary for the penetration of HIV into the cells. Macrophages serve as the main reservoir of HIV and may carry the virus to different organs. The prolonged latent period may be ascribed to cytotoxic lymphocytes specifically active against HIV and suppressing its replication. The progress of the disease is due to viral and cellular factors and depends on the functional changes in T-cells, B-cells, macrophages, the formation of immune complexes, the presence of stimulating antibodies and autoimmune phenomena.     

Infection caused by the human immunodeficiency virus type 2 in the USSR

The serological study of 20 sera, showing atypical reaction with HIV-1 in the immunoblotting assay, for the presence of HIV-2 infection revealed some cases of this infection among Africans who had arrived to the USSR from Western Africa (5 cases) and Burundi (1 case); besides, in 1 case HIV-2 infection was detected in a Soviet female citizen having had many sexual partners among foreigners.     

Mutation and control of the human immunodeficiency virus

We examine the dynamics of infection by the human immunodeficiency virus (HIV), as well as therapies that minimize viral load, restore adaptive immunity, and use minimal dosage of anti-HIV drugs. Virtual therapies for wild-type infections are demonstrated; however, the HIV infection is never cured, requiring continued treatment to keep the condition in remission. With high viral turnover and mutation rates, drug-resistant strains of HIV evolve quickly. The ability of optimal therapy to contain drug-resistant strains is shown to depend upon the relative fitness of mutant strains.     

The epidemiology of the infection caused by the human immunodeficiency virus in the USSR

The existing system of the epidemiological surveillance of HIV infection in the USSR makes it possible to evaluate the present situation as the beginning of epidemic. The main routes of the transfer of HIV infection as per data for April 1989: 50% by the sexual route, 25.8% by parenteral manipulations.     

Satellite RNA for the control of plant diseases caused by cucumber mosaic virus

Two virus-protecting strains, S₅₁ and S₅₂, were obtained for the control of cucumber mosaic virus (CMV) by local lesion selection after adding satellite RNA to the RNA genome of CMV. Both were found to protect pepper plants against a virulent strain of CMV under greenhouse and field conditions. Results from 14 localities in China indicated that the use of protective strains decreased the disease index by 21.6% to 82.8% and increased fruit yields by 10.8% to 55.6%. The host reactions and safety of S₅₁ and S₅₂ were tested, and the effects of the strains on plant growth were also investigated. Possible mechanisms of control of CMV-caused plant diseases by mild strains are discussed.     

The lymphocyte populations at different stages in the infection caused by the human immunodeficiency virus

In 58 persons infected with HIV the comparative study of the content of immunocompetent cells was carried out by the methods of rosette formation and immunofluorescence with the use of monoclonal antibodies. An increase in the content of rosette-forming cells (RFC), such as active E-RFC, E-RFC, theophylline-resistant E-RFC and M-FRC, in asymptomatic seropositive persons was established. At this stage of the disease the amount of lymphocytes T4 and T8 and their ratio underwent no essential changes. At the stage of lymphoadenopathy an increase in the content of lymphocytes T8, more pronounced in patients with secondary infectious lesions, was noted. At this stage a decrease in T4/T8 ratio appeared for the first time. A high level of rosette-forming lymphocytes was still observed both at this period and at the period of clinically developed AIDS, while the level of lymphocytes T4 sharply dropped in such patients.     

Closing the door to human immunodeficiency virus

The pandemic of human immunodeficiency virus type one (HIV-1), the major etiologic agent of acquired immunodeficiency disease (AIDS), has led to over 33 million people living with the virus, among which 18 million are women and children. Until now, there is neither an effective vaccine nor a therapeutic cure despite over 30 years of efforts. Although the Thai RV144 vaccine trial has demonstrated an efficacy of 31.2%, an effective vaccine will likely rely on a breakthrough discovery of immunogens to elicit broadly reactive neutralizing antibodies, which may take years to achieve. Therefore, there is an urgency of exploring other prophylactic strategies. Recently, antiretroviral treatment as prevention is an exciting area of progress in HIV-1 research. Although effective, the implementation of such strategy faces great financial, political and social challenges in heavily affected regions such as developing countries where drug resistant viruses have already been found with growing incidence. Activating latently infected cells for therapeutic cure is another area of challenge. Since it is greatly difficult to eradicate HIV-1 after the establishment of viral latency, it is necessary to investigate strategies that may close the door to HIV-1. Here, we review studies on non-vaccine strategies in targeting viral entry, which may have critical implications for HIV-1 prevention.     

Concerning the early and current spread of human immunodeficiency virus type 1 and the scientific burden of proof versus the burden of current human immunodeficiency virus incidence

The following points were made during the Discussion that followed the paper by Brian Martin.     

Extremely rapid spread of human immunodeficiency virus type 1 BF recombinants in Argentina

The epidemic of human immunodeficiency virus type 1 (HIV-1) in Argentina is distinctive in that many infections are caused by subtype BF recombinant viruses. To determine their demographic history, we estimated the evolutionary rate, mode of population growth, and age of genetic diversity among 40 BF vpu sequences. This revealed one of the highest substitution rates reported for HIV-1, at 10.793 x 10(-3) substitutions per site per year, and a very rapid rate of population growth, with an initial mean epidemic doubling time of 3.72 months. This rapid population growth is compatible with an elevated fitness for subtype BF compared to that for "pure" B and F viruses.     

Complement activation by human monoclonal antibodies to human immunodeficiency virus.

It has been shown that the incubation of human immunodeficiency virus (HIV) with polyclonal antibodies from HIV-infected persons and complement results in complement-mediated neutralization due, at least in part, to virolysis. The current study was performed to determine whether any of a panel of 16 human monoclonal antibodies to HIV could activate complement and, if so, which determinants of the HIV envelope could serve as targets for antibody-dependent complement-mediated effects. Human monoclonal antibodies directed to the third variable region (V3 region) of HIVMN gp120 induced C3 deposition on infected cells and virolysis of free virus. Antibodies to two other sites on HIVMN gp120 and two sites on gp41 induced few or no complement-mediated effects. Similarly, only anti-V3 antibodies efficiently caused complement-mediated effects on the HIVIIIB isolate. In general, the level of C3 deposition on infected cells paralleled the relative level of bound monoclonal antibodies. As expected, pooled polyclonal antibodies from infected persons were much more efficient than monoclonal antibodies inducing C3 deposition per unit of bound immunoglobulin. Treatment of virus or infected cells with soluble CD4 resulted in increases in anti-gp41 antibody-mediated virolysis and C3 deposition but decreases in anti-V3 antibody-mediated virolysis and C3 deposition. In general, virolysis of HIV was more sensitive as an indicator of complement-mediated effects than infected-cell surface C3 deposition, suggesting the absence of or reduced expression of functional complement control proteins on the surface of free virus. Thus, this study shows that human monoclonal antibodies to the V3 region of gp120 are most efficient in causing virolysis of free virus and C3 deposition on infected cells. Elution of gp120 with soluble CD4 exposes epitopes on gp41 that can also bind antibody, resulting in virolysis and C3 deposition. These findings establish a serologically defined model system for the further study of the interaction of complement and HIV.     

Patterns of spread of Carrot virus Y in carrot plantings and validation of control measures

Patterns of spread of Carrot virus Y (CarVY) were examined in carrot plantings in Western Australia into which naturally occurring aphid vectors spread the virus from external infection sources. Within three field trials, CarVY ‘infector’ plants were introduced between or at different distances from carrot plantings. There was a marked decline in CarVY incidence over distance from adjacent introduced infection sources. Clusters of infected plants that enlarged and coalesced were concentrated next to such sources but, later, isolated, expanding clusters formed further away. With a small external virus source, initial spread into the edge of a planting was less extensive than with a larger source. When 15‐m‐wide fallow areas separated a CarVY source from carrot plots, spread was much slower than when the separation was only 1 m; it was also slower upwind than downwind of this source. The data collected help validate the inclusion of isolation and ‘safe’ planting distances, intervening fallow, planting upwind, prompt removal of virus sources, avoidance of side‐by‐side plantings and manipulation of planting date within an integrated disease management strategy for CarVY in carrots.     

Serial human passage of simian immunodeficiency virus by unsterile injections and the emergence of epidemic human immunodeficiency virus in Africa

There is compelling evidence that both human immunodeficiency virus (HIV) types emerged from two dissimilar simian immunodeficiency viruses (SIVs) in separate geographical regions of Africa. Each of the two HIVs has its own simian progenitor and specific genetic precursor, and all of the primates that carry these SIVs have been in close contact with humans for thousands of years without the emergence of epidemic HIV. To date no plausible mechanism has been identified to account for the sudden emergence in the mid-20th century of these epidemic HIVs. In this study we examine the conditions needed for SIV to complete the genetic transition from individual human SIV infections to epidemic HIV in humans. The genetic distance from SIV to HIV and the mutational activity needed to achieve this degree of adaptation to human hosts is placed within a mathematical model to estimate the probabilities of SIV completing this transition within a single SIV-infected human host. We found that the emergence of even one epidemic HIV strain, following a single human exposure to SIV, was very unlikely. And the probability of four or more such transitions (i.e. HIV-1 groups M, O and HIV-2 subtypes A and B) occurring in a brief period is vanishingly small. We conclude that SIV cannot become a zoonosis, but requires adaptive mutations to become HIV. Some modern event must have aided in the transition of SIV to HIV. Our research indicates that serial passage of partially adapted SIV between humans could produce the series of cumulative mutations sufficient for the emergence of epidemic HIV strains. We examined the rapid growth of unsterile injections in Africa beginning in the 1950s as a biologically plausible event capable of greatly increasing serial human passage of SIV and generating HIV by a series of multiple genetic transitions. We conclude that increased unsterile injecting in Africa during the period 1950-1970 provided the agent for SIV human infections to emerge as epidemic HIV in the modern era.     

An in vitro rapid-turnover assay for human immunodeficiency virus type 1 replication selects for cell-to-cell spread of virus

We have developed a rapid-turnover culture system where the life span of a human immunodeficiency virus type 1-infected cell is controlled by periodic addition of a cytotoxic agent, mitomycin C. These mitomycin C-exposed cells are cocultured with a constant number of uninfected cells as new targets for the virus. Passage of the virus-infected cells under these conditions led to the emergence of a viral variant that was able to replicate efficiently in this culture system. After biologic and molecular cloning, we were able to identify a single frameshift mutation in the vpu open reading frame that was sufficient for growth of the mutant virus in the rapid-turnover assay. This virus variant spread more efficiently by cell-to-cell transfer than the parental virus did. Electron micrographs of cells infected with the delta vpu virus revealed a large number of mature viral capsids attached to the plasma membrane. The presence of these mature virus particles on the cell surface led to enhanced fusion and formation of giant syncytia with uninfected cells. Enhanced cell-to-cell transfer of the delta vpu virus provides an explanation for the survival of this mutant virus in the rapid-turnover culture system. The in vitro rapid-turnover culture system is a good representation of the in vivo turnover kinetics of infected cells and their continual replacement by host lymphopoietic mechanisms.