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PubMed1996

[Thrombotic microangiopathies in HIV infection: 4 cases].

Thrombotic microangiopathy (TMA) has been rarely described in HIV-infected patients. We report four cases of TMA during HIV infection and we analyse clinical, biological, etiologic, therapeutic and evolutive aspects of these four cases. Initial symptomatology is non specific and diagnosis is often delayed. Peripheric thrombopenia with haemolytic anemia and renal failure must be suggestive of the diagnosis. TMA can be present at any stage of HIV infection. Physiopathological mechanism of TMA during HIV infection remains unclear. These cases lead to suspect the role of opportunistic infections, neoplasia or HIV directly by endothelial injury or indirectly by cytokines secretion. Therapy of TMA is not different from non-HIV patients. Improvement with treatment must be obtained but long-term prognosis remains poor in account of HIV infection.

Adult↗
PubMed2000

The role of antiretrovirals and drug resistance in vertical transmission of HIV-1 infection.

Large-cohort studies in North America, Europe, and Thailand have shown that zidovudine/azidothymidine (AZT) monotherapy, given at the late stages of pregnancy, is of proven benefit in reducing mother-to-infant HIV transmission by 51% to 68%. AZT monotherapy will not be of long-term benefit for mothers because no single drug can counteract viral infection; benefits to babies will be short-lived if HIV-1 is acquired through breastfeeding after birth. Unfortunately, ongoing mutation of HIV under conditions of drug pressure allows for the evolution and selection of AZT-resistant viruses. Emergence of AZT-resistant variants in pregnant mothers (7-29%) and their infected offspring (5-21%) has been described in several studies. Drug resistance arises more frequently in those mothers who received AZT therapy before pregnancy. Recent advances in combination chemotherapy may provide alternative strategies in prevention of vertical transmission and drug resistance. Genotypic screening of the HIV-1 isolated from pregnant mothers may provide rational modifications in antiretroviral (ARV) strategies to circumvent vertical HIV transmission. This may be of advantage for resource-rich nations but not for underdeveloped nations with limited access to ARVs. Public health programs are vital to have an impact on the tragic pandemic of pediatric AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed2007

Evolution of CXCR4-using human immunodeficiency virus type 1 SF162 is associated with two unique envelope mutations.

CCR5-using human immunodeficiency virus type 1 (HIV-1) isolates typically gain CXCR4 use via multiple mutations in V3 and often V1/V2 regions of envelope, and patterns of mutations are distinct for each isolate. Here, we report that multiple CXCR4-using variants of a parental CCR5-using HIV-1 isolate, SF162, obtained by either target cell selection or CCR5 inhibition have a common mutation pattern characterized by the same two V3 mutations and that these mutations preexisted in some of the SF162 stocks. These results imply that SF162 has a single pathway for acquiring CXCR4 use and that prolonged culture is sufficient to select for R5X4 variants.

Cells, Cultured↗
PubMed2005

An immune control model for viral replication in the CNS during presymptomatic HIV infection.

The brain is targeted by human immunodeficiency virus type 1 (HIV-1) during the course of untreated infection, leading to cognitive impairment, neurological damage and HIV encephalitis (HIVE). To study early dynamics of HIV entry into the brain, we examined a unique autopsy series of samples obtained from 15 untreated individuals who died in the presymptomatic stages of infection from non-HIV causes. HIV was detected and quantified by limiting dilution PCR and genetically characterized in the V3 region of env. Limiting dilution was shown to be essential for correct estimation of genetic partitioning between brain- and lymphoid-associated HIV populations. While no actively expressing HIV-infected cells were detected by immunohistochemistry, variable and generally extremely low levels of proviral DNA were detected in presymptomatic brain samples. V3 region sequences were frequently genetically distinct from lymphoid-associated HIV variants, with association index (AI) values similar to those observed in cases of HIVE. Infiltration of CD8 lymphocytes in the brain was strongly associated with expression of activation markers (MHCII; R = 0.619; P < 0.05), the presence of HIV-infected cells (proviral load; R = 0.608; P < 0.05) and genetic segregation of brain variants from populations in lymphoid tissue (AI value, R = -0.528; P approximately 0.05). CD8 lymphocytes may thus limit replication of HIV seeded into the brain in early stages of infection. Neurological complications in AIDS occur when this control breaks down, due to systemic immunosuppression from HIV that destroys CD8 lymphocyte function and/or through the evolution of more aggressive neuropathogenic variants.

Adult↗
PubMed1997

Human immunodeficiency virus type 1 genetic evolution in children with different rates of development of disease.

The rate of development of disease varies considerably among human immunodeficiency virus type 1 (HIV-1)-infected children. The reasons for these observed differences are not clearly understood but most probably depend on the dynamic interplay between the HIV-1 quasispecies virus population and the immune constraints imposed by the host. To study the relationship between disease progression and genetic diversity, we analyzed the evolution of viral sequences within six perinatally infected children by examining proviral sequences spanning the C2 through V5 regions of the viral envelope gene by PCR of blood samples obtained at sequential visits. PCR product DNAs from four sample time points per child were cloned, and 10 to 13 clones from each sample were sequenced. Greater genetic distances relative to the time of infection were found for children with low virion-associated RNA burdens and slow progression to disease relative to those found for children with high virion-associated RNA burdens and rapid progression to disease. The greater branch lengths observed in the phylogenetic reconstructions correlated with a higher accumulation rate of nonsynonymous base substitutions per potential nonsynonymous site, consistent with positive selection for change rather than a difference in replication kinetics. Viral sequences from children with slow progression to disease also showed a tendency to form clusters that associated with different sampling times. These progressive shifts in the viral population were not found in viral sequences from children with rapid progression to disease. Therefore, despite the HIV-1 quasispecies being a diverse, rapidly evolving, and competing population of genetic variants, different rates of genetic evolution could be found under different selective constraints. These data suggest that the evolutionary dynamics exhibited by the HIV-1 quasispecies virus populations are compatible with a Darwinian system evolving under the constraints of natural selection.

Amino Acid Sequence↗
PubMed1996

The variety of human virus evolution.

There have been many wise suggestions of ways that evolution may occur but those ways seem often hard to support with good examples. Viruses have proven to be replete with some of these items. This paper reviews work that shows: (1) very fast rates of evolution; (2) positive Darwinian selection with the selective pressure specifically identified; (3) viral reassortment; (4) grossly unequal rates of evolution depending upon the host of the virus; (5) accurate dating of the cenancestor, the most recent common ancestor; (6) correspondence between the evolutionary tree and the geography of the place of isolation; (7) punctuated molecular evolution; and (8) network evolution.

Animals↗
PubMed1989

Weights for data related by a tree.

How can one characterize a set of data collected from different biological species, or indeed any set of data related by an evolutionary tree? The structure imposed by the tree implies that the data are not independent, and for most applications this should be taken into account. We describe strategies for weighting the data that circumvent some of the problems of dependency.

Animals↗
PubMed1994

Convergent evolution: the need to be explicit.

Convergence as a phenomenon in molecular evolution is an issue that confuses many discussions. Often the problem is that not enough care is taken to state exactly what kind of convergence one has in mind. Functional and mechanistic convergence are both common, and some structural convergence has probably occurred, but a convincing case for genuine sequence convergence has yet to be made.

Amino Acid Sequence↗
PubMed1994

Serological diagnosis of HTLV-I/II infections in France.

During the last years, important improvements have been made in the field of HTLV-I/II serodiagnosis. The screening tests, which combine higher performances of the sensitivity towards HTLV-I and HTLV-II samples, and better specificity, are manifold. The criteria of positivity by western-blots have been reinforced. As for HIV, some western-blot profiles with no evolution on two successive samples, correspond to non specific HTLV reactions. HTLV-I/II serotyping is easier than before. More effective tools will certainly be available in the coming years for the Blood Transfusion Services and the physicians.

Blotting, Western↗
PubMed2006

Correlation between SIV Tat evolution and AIDS progression in cerebrospinal fluid of morphine-dependent and control macaques infected with SIV and SHIV.

Morphine abuse has been associated with higher virus replication and accelerated disease progression in a non-human primate model of AIDS. In our previous report, we have shown that 50% of morphine-addicted macaques progress rapidly and that 2/3 of the rapid progressors exhibit severe neuropathogenesis. In this report, we examined the sequence evolution of the SIV Tat protein, known to participate in AIDS neuropathology, in the cerebrospinal fluid (CSF) of morphine-dependent and control macaques over the first 20 weeks of infection. The CSF SIV Tat evolution was found to be inversely related with disease progression, and the highly neuropathogenic inoculum clone sequence was the prevalent CSF form in rapid progressors. Divergence from the inoculum clone was significantly greater in both morphine-dependent normal progressors and control macaques than in the morphine-dependent rapid progressors. Furthermore, we also found evidence of a trend that morphine alters the type of mutation, resulting in an enhanced ratio of transitions to transversions (Ts:Tv). Rapid disease exacerbates this trend and appears to influence the distribution of nonsynonymous changes in the first exon of SIV tat, with a clear majority of mutations occurring in the C-terminal half of the protein where the known functionally important domains reside. Thus, morphine abuse may change the nature and extent of mutations that drive viral evolution.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Cloning and sequencing of ISC1041 from the archaeon Sulfolobus solfataricus MT-4, a new member of the IS30 family of insertion elements.

A genomic fragment containing the insertion sequence ISC1041 has been cloned by PCR from the archaeon Sulfolobus solfaricus MT-4, an extremophilic microorganism which grows at 87 degrees C. The 1038 bp ISC1041 element contains an imperfect 18 nt repeat and a long open reading frame which encodes a polypeptide of 311 amino acid residues. The translated amino acid sequence shows a significant similarity to IS30-like transposases. Structural analysis indicates that ISC1041 is a novel member of the IS30 family and displays the DDE motif not previously seen in Archaea. This motif is believed to be involved in the integration mechanism of many mobile elements. As this motif is present in several integrases and transposases which, despite the lack of overall protein homologies, share topological homologies to the DDE motif, a common ancestor has been proposed. The finding of an IS30-like transposase in the archaeal kingdom may have relevance for horizontal gene transfer.

Amino Acid Sequence↗
PubMed1999

Human immunodeficiency viruses in the developing world.

AIDS has become a major burden in developing countries. At present, more than 90% of new HIV infections are emerging in Asia and Africa. Particularly ominous is the epidemic due to HIV-1 C in southern Africa, where about 25% of adults in several countries are infected. Although most of its spread apparently occurred during the 1990s, HIV-1 C currently accounts for one-half of the infections in the world. Both HIV-2, which is less virulent than HIV-1, and HIV-1 apparently spread to the human population from nonhuman African primates during the twentieth century. HIV-1 infection is usually lethal in the absence of antiretroviral therapy, but clinical disease occurs only after an induction period of several years. Some subtypes of HIV-1, such as C, E, and A, appear to be transmitted more efficiently than HIV-1 B, which is the major subtype in the United States and Europe. Molecular evolutionary changes that include receptor affinity, mediated by the env gene, and increased transcriptional activation, mediated by changes in the LTR and the tat gene, may account for some of the changes in transmission. Current therapies are prohibitively expensive for use in adults in most developing countries, although drugs for maternal-to-infant transmission are becoming accessible. A vaccine for HIV is desperately needed for the developing world.

Animals↗
PubMed2006

Primary human immunodeficiency virus type 1 infection: clinical, virological and immunological characteristics of 75 patients (1997-2003).

OBJECTIVES: To describe the epidemiological and clinical characteristics and the evolution of a cohort of patients with primary HIV-1 infection from the Barcelona area. METHODS: Prospective cohort study of HIV-infected patients diagnosed with primary HIV infection in a tertiary hospital in Barcelona (Spain) from 1997 through 2003. Descriptive analysis of epidemiological and clinical characteristics and effect of highly active antiretroviral treatment (HAART) on outcome. RESULTS: A total of 75 patients were diagnosed, accounting for 2.9% of the total of newly diagnosed HIV patients during the same time period. Eighty-one percent of the patients were males and the median age was 30 years (IQR 26-38). The most frequent transmission route was homosexual (72%), followed by heterosexual (17%) and intravenous drug abuse (11%). Seventy-seven percent of patients presented symptoms, the most frequent being fever (98%), asthenia (86%), arthralgia-myalgia (65%), lymphadenopathy (55%), night sweats (48%) and rash. Sixty-five percent started HAART, although the proportion of patients that received HAART decreased from 79% during the period 1997-2000 to 49% during the period 2001-2003 (p < 0.01). After a median follow-up of 37 months (IQR 26-66), one patient died and eight cases were lost to follow-up. The patients who did not receive HAART had a higher probability of immunological or clinical deterioration during the follow-up when compared to the group that received HAART (42.3% versus 12.3%; p < 0.001). In treated patients, dyslipidemia and lipodystrophy were diagnosed in 58% and 37% of cases, respectively. CONCLUSIONS: Primary HIV-1 infection was diagnosed more frequently in homosexual males, and its clinical characteristics were similar to those observed in previous studies. HAART given during primary HIV infection was effective, but was associated with a high percentage of adverse effects.

Adult↗
PubMed1996

Can evolutionary principles help resolve the acquired immune deficiency syndrome crisis?

The population of retroviruses inside each infected host can quickly adapt its genes in response to survival threats. For this reason, therapeutics attempting to eliminate or inhibit the human immunodeficiency virus have been unsuccessful. However, it may be possible to apply evolutionary principles to the problem of human immunodeficiency virus infection/acquired immune deficiency syndrome. The rapid evolution capabilities of this pathogen might assist researchers in evolving human immunodeficiency virus toward the goal of virus-host coexistence. In this relationship, infecting viruses do not harm their host. Two different examples illustrate the theoretical application of evolutionary principles to this problem. First, by viewing the virus as a new gene of the immune system, it is possible to evolve this gene toward the goal of improving immune function. Second, the retroviral population of each host is maladapted for long-term survival. Retroviral genes could be evolved with respect to continued existence in the host.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Site stripping based on likelihood ratio reduction is a useful tool to evaluate the impact of non-clock-like behavior on viral phylogenetic reconstructions.

The site stripping for clock detection procedure was implemented in the recently developed maximum likelihood framework for estimating evolutionary rates and divergence times in measurably evolving populations. The method was used to investigate the effect of rate variability on estimating divergence times in non-clock-like trees for human immunodeficiency viruses and hepatitis C viruses. We validate our approach by comparing dated coalescent nodes in molecular phylogenies with known dates of transmission. Our method was able to rapidly recover clock-like behavior and to indicate the presence and direction of a bias when estimates of divergence times using the unstripped data were flawed.

Algorithms↗